JoAnne L Flynn

Summary

Affiliation: University of Pittsburgh
Country: USA

Publications

  1. ncbi What's good for the host is good for the bug
    JoAnne L Flynn
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
    Trends Microbiol 13:98-102. 2005
  2. ncbi Immunology of tuberculosis and implications in vaccine development
    JoAnne L Flynn
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, W1157 Biomedical Science Tower, Pittsburgh, PA 15261, USA
    Tuberculosis (Edinb) 84:93-101. 2004
  3. pmc The mutation rate of mycobacterial repetitive unit loci in strains of M. tuberculosis from cynomolgus macaque infection
    Mark N Ragheb
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA
    BMC Genomics 14:145. 2013
  4. ncbi Immune responses in tuberculosis
    J L Flynn
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    Curr Opin Immunol 12:432-6. 2000
  5. ncbi Lessons from experimental Mycobacterium tuberculosis infections
    JoAnne L Flynn
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh PA 15261, USA
    Microbes Infect 8:1179-88. 2006
  6. pmc Macrophages and control of granulomatous inflammation in tuberculosis
    J L Flynn
    Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Mucosal Immunol 4:271-8. 2011
  7. ncbi Immune evasion by Mycobacterium tuberculosis: living with the enemy
    JoAnne L Flynn
    Department of Molecular Genetics and Biochemistry, W1157 Biomedical Science Tower, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    Curr Opin Immunol 15:450-5. 2003
  8. ncbi Immunology of tuberculosis
    J L Flynn
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    Annu Rev Immunol 19:93-129. 2001
  9. ncbi Non-human primates: a model for tuberculosis research
    J L Flynn
    Department of Molecular Genetics and Biochemistry, W1157 Biomedical Science Tower, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    Tuberculosis (Edinb) 83:116-8. 2003
  10. pmc Quantitative comparison of active and latent tuberculosis in the cynomolgus macaque model
    Philana Ling Lin
    Department of Pediatrics, Children s Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15224, USA
    Infect Immun 77:4631-42. 2009

Research Grants

  1. A NON-HUMAN PRIMATE MODEL OF TUBERCULOSIS AND AIDS
    Joanne Flynn; Fiscal Year: 2004
  2. CD4 T Cells in Tuberculosis
    Joanne Flynn; Fiscal Year: 2006
  3. FUNCTION OF CD8 T CELLS IN TUBERCULOSIS
    Joanne Flynn; Fiscal Year: 2006
  4. Immunology of Infectious Disease
    Joanne Flynn; Fiscal Year: 2007
  5. Latent and Reactivation Tuberculosis
    Joanne Flynn; Fiscal Year: 2007
  6. FUNCTION OF CD8 T CELLS IN TUBERCULOSIS
    Joanne Flynn; Fiscal Year: 2009
  7. CD4 T Cells in Tuberculosis
    JoAnne L Flynn; Fiscal Year: 2010
  8. FUNCTION OF CD8 T CELLS IN TUBERCULOSIS
    JoAnne L Flynn; Fiscal Year: 2010
  9. CD4 T Cells in Tuberculosis
    JoAnne L Flynn; Fiscal Year: 2011
  10. FUNCTION OF CD8T CELLS IN TUBERCULOSIS
    Joanne Flynn; Fiscal Year: 2001

Collaborators

Detail Information

Publications61

  1. ncbi What's good for the host is good for the bug
    JoAnne L Flynn
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
    Trends Microbiol 13:98-102. 2005
    ....
  2. ncbi Immunology of tuberculosis and implications in vaccine development
    JoAnne L Flynn
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, W1157 Biomedical Science Tower, Pittsburgh, PA 15261, USA
    Tuberculosis (Edinb) 84:93-101. 2004
    ..Studying both the host and the pathogen will elucidate potential vaccine candidates. In this review, the known functions of immune components in the response to M. tuberculosis and implications for vaccine development will be discussed...
  3. pmc The mutation rate of mycobacterial repetitive unit loci in strains of M. tuberculosis from cynomolgus macaque infection
    Mark N Ragheb
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA
    BMC Genomics 14:145. 2013
    ..From these data, we have estimated the rate of MIRU variation in the host environment, providing a benchmark rate for future epidemiologic work...
  4. ncbi Immune responses in tuberculosis
    J L Flynn
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    Curr Opin Immunol 12:432-6. 2000
    ....
  5. ncbi Lessons from experimental Mycobacterium tuberculosis infections
    JoAnne L Flynn
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh PA 15261, USA
    Microbes Infect 8:1179-88. 2006
    ..The careful and thoughtful use of animal models is essential to furthering our understanding of M. tuberculosis, and this knowledge will enhance the discovery of improved treatment and prevention strategies...
  6. pmc Macrophages and control of granulomatous inflammation in tuberculosis
    J L Flynn
    Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Mucosal Immunol 4:271-8. 2011
    ..tuberculosis. In this review, we focus on the key role of the macrophage in balancing inflammation in the granuloma...
  7. ncbi Immune evasion by Mycobacterium tuberculosis: living with the enemy
    JoAnne L Flynn
    Department of Molecular Genetics and Biochemistry, W1157 Biomedical Science Tower, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    Curr Opin Immunol 15:450-5. 2003
    ..M. tuberculosis also modulates antigen presentation to prevent the detection of infected macrophages by CD4(+) T cells...
  8. ncbi Immunology of tuberculosis
    J L Flynn
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    Annu Rev Immunol 19:93-129. 2001
    ..The pace of this research must be maintained if we are to realize an effective vaccine in the next decades...
  9. ncbi Non-human primates: a model for tuberculosis research
    J L Flynn
    Department of Molecular Genetics and Biochemistry, W1157 Biomedical Science Tower, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    Tuberculosis (Edinb) 83:116-8. 2003
    ....
  10. pmc Quantitative comparison of active and latent tuberculosis in the cynomolgus macaque model
    Philana Ling Lin
    Department of Pediatrics, Children s Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15224, USA
    Infect Immun 77:4631-42. 2009
    ..Finally, we have observed a spectrum of disease not only in monkeys with active disease but also in those with latent infection that provides insight into human latent tuberculosis...
  11. pmc Tumor necrosis factor neutralization results in disseminated disease in acute and latent Mycobacterium tuberculosis infection with normal granuloma structure in a cynomolgus macaque model
    Philana Ling Lin
    Children s Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, PA, USA
    Arthritis Rheum 62:340-50. 2010
    ..This study was undertaken to investigate immune modulation in the setting of TNF neutralization in primary and latent tuberculosis in a non-human primate model...
  12. pmc Early events in Mycobacterium tuberculosis infection in cynomolgus macaques
    Philana Ling Lin
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, W1157 Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA 15261, USA
    Infect Immun 74:3790-803. 2006
    ..From these studies, we conclude that immune responses to M. tuberculosis are relatively slow in the local and peripheral compartments and that necrosis occurs surprisingly quickly during granuloma formation...
  13. ncbi Experimental Pneumocystis carinii pneumonia in simian immunodeficiency virus-infected rhesus macaques
    Kathryn F Board
    Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Infect Dis 187:576-88. 2003
    ..The animals had a protracted period of asymptomatic colonization with P. carinii before progression to PCP. The development of a model of PCP in SIV-infected rhesus macaques provides the means to study AIDS-associated PCP...
  14. pmc Reactivation of latent tuberculosis in cynomolgus macaques infected with SIV is associated with early peripheral T cell depletion and not virus load
    Collin R Diedrich
    Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America
    PLoS ONE 5:e9611. 2010
    ..Granulomas from these animals demonstrated histopathologic characteristics consistent with a chronically active disease process. These results suggest initial T cell depletion may strongly influence outcomes of HIV-Mtb co-infection...
  15. pmc Simian immunodeficiency virus-induced changes in T cell cytokine responses in cynomolgus macaques with latent Mycobacterium tuberculosis infection are associated with timing of reactivation
    Joshua T Mattila
    Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    J Immunol 186:3527-37. 2011
    ..Moreover, it appears that mycobacteria-specific multifunctional T cells are better correlates of Ag load (i.e., disease status) than of protection...
  16. pmc Microenvironments in tuberculous granulomas are delineated by distinct populations of macrophage subsets and expression of nitric oxide synthase and arginase isoforms
    Joshua T Mattila
    Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15261, USA
    J Immunol 191:773-84. 2013
    ..Together, these data support the concept that granulomas have organized microenvironments that balance antimicrobial anti-inflammatory responses to limit pathology in the lungs. ..
  17. pmc CD4 T cell depletion exacerbates acute Mycobacterium tuberculosis while reactivation of latent infection is dependent on severity of tissue depletion in cynomolgus macaques
    Philana Ling Lin
    Department of Pediatrics, Children s Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, PA, USA
    AIDS Res Hum Retroviruses 28:1693-702. 2012
    ..CD4 depletion influences CD8 T cell function. This study has important implications for human HIV-M. tuberculosis coinfection...
  18. pmc Activated B cells in the granulomas of nonhuman primates infected with Mycobacterium tuberculosis
    Jia Yao Phuah
    Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    Am J Pathol 181:508-14. 2012
    ..tuberculosis antigens at the site of infection, including lung granulomas and thoracic lymph nodes. These antibodies likely have the capacity to modulate local control of infection in tissues...
  19. pmc CD4(+) regulatory T cells in a cynomolgus macaque model of Mycobacterium tuberculosis infection
    Angela M Green
    Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Infect Dis 202:533-41. 2010
    ..We sought to determine whether a higher frequency of regulatory T (T(reg)) cells predispose an individual toward active disease or whether T(reg) cells develop in response to active disease...
  20. ncbi Long-term control of Mycobacterium tuberculosis infection is mediated by dynamic immune responses
    Vanja Lazarevic
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261, USA
    J Immunol 175:1107-17. 2005
    ..Ag dose could potentially govern the functional program of CD8(+) T cells. Collectively, these results depict a host immune response mounted against M. tuberculosis of a significantly more dynamic nature than previously recognized...
  21. pmc Induction of Mycobacterium tuberculosis-specific primary and secondary T-cell responses in interleukin-15-deficient mice
    Vanja Lazarevic
    Department of Molecular Genetics and Biochemistry, W1157 Biomedical Science Tower, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261, USA
    Infect Immun 73:2910-22. 2005
    ..tuberculosis challenge. These findings demonstrate that efficient effector CD4 and CD8 T cells can be developed following M. tuberculosis infection in the absence of IL-15 but that recall T-cell responses may be impaired...
  22. pmc In situ study of abundant expression of proinflammatory chemokines and cytokines in pulmonary granulomas that develop in cynomolgus macaques experimentally infected with Mycobacterium tuberculosis
    Craig L Fuller
    Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA
    Infect Immun 71:7023-34. 2003
    ..These results suggest that expression of CXCR3 ligands and the subsequent recruitment of CXCR3(+) cells are involved in granuloma formation and maintenance...
  23. ncbi TNF influences chemokine expression of macrophages in vitro and that of CD11b+ cells in vivo during Mycobacterium tuberculosis infection
    Holly M Scott Algood
    Department of Molecular Genetics and Biochemistry and Molecular Virology and Microbiology Graduate Program, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    J Immunol 172:6846-57. 2004
    ..Therefore, TNF affects the expression of chemokines by macrophages in vitro and CD11b(+) cells in vivo, which probably influences the local chemokine gradients and granuloma formation...
  24. pmc Interleukin-12 therapy reduces the number of immune cells and pathology in lungs of mice infected with Mycobacterium tuberculosis
    Dawn Nolt
    Division of Allergy, Immunology, and Infectious Diseases, Children s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    Infect Immun 72:2976-88. 2004
    ..IL-12 therapy reduced the pathology of M. tuberculosis-infected lungs, as granulomas were smaller and less numerous. These studies support an immunoregulatory role for IL-12 in tuberculosis...
  25. ncbi Tumor necrosis factor and tuberculosis
    Philana Ling Lin
    Department of Pediatrics, Children s Hospital, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    J Investig Dermatol Symp Proc 12:22-5. 2007
    ..We are using animal models to understand how TNF neutralization by these drugs can lead to reactivation of tuberculosis...
  26. pmc Monocyte-derived IL-5 reduces TNF production by Mycobacterium tuberculosis-specific CD4 T cells during SIV/M. tuberculosis coinfection
    Collin R Diedrich
    Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    J Immunol 190:6320-8. 2013
    ..Specifically, reductions in the frequency of TNF-producing M. tuberculosis-specific CD4 T cells were caused, at least in part, by SIV-induced production of monocyte derived IL-5...
  27. pmc The multistage vaccine H56 boosts the effects of BCG to protect cynomolgus macaques against active tuberculosis and reactivation of latent Mycobacterium tuberculosis infection
    Philana Ling Lin
    Department of Pediatrics, Children s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
    J Clin Invest 122:303-14. 2012
    ..Our results indicate that H56/IC31 boosting is able to control late-stage infection with M. tuberculosis and contain latent tuberculosis, providing a rationale for the clinical development of H56...
  28. ncbi Abatacept treatment does not exacerbate chronic Mycobacterium tuberculosis infection in mice
    Carolyn L Bigbee
    University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261, USA
    Arthritis Rheum 56:2557-65. 2007
    ..We undertook this study to determine the effect of abatacept treatment in a murine model of chronic M tuberculosis infection...
  29. pmc Comparison of the effects of pathogenic simian human immunodeficiency virus strains SHIV-89.6P and SHIV-KU2 in cynomolgus macaques
    Santosh N Pawar
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    AIDS Res Hum Retroviruses 24:643-54. 2008
    ..SHIV-89.6P induced more IFN-gamma expression than SHIV-KU2. These results indicate SHIV-89.6P and SHIV-KU2 infect cynomolgus macaques and may be used to accurately model effects of HIV infection on latent TB...
  30. ncbi Neutralization of tumor necrosis factor (TNF) by antibody but not TNF receptor fusion molecule exacerbates chronic murine tuberculosis
    Hillarie L Plessner
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    J Infect Dis 195:1643-50. 2007
    ..These findings begin to clarify the mechanistic difference between anti-TNF agents and their role in the exacerbation of tuberculosis...
  31. ncbi Tumor necrosis factor and chemokine interactions in the formation and maintenance of granulomas in tuberculosis
    Holly M Scott Algood
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    Clin Infect Dis 41:S189-93. 2005
    ..Chemokines are small molecules that direct the migration of cells within the body. Our data support the notion that TNF is required for appropriate chemokine expression by M. tuberculosis-infected macrophages, both in vitro and in vivo...
  32. pmc Inoculation dose of Mycobacterium tuberculosis does not influence priming of T cell responses in lymph nodes
    Amy J Myers
    Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    J Immunol 190:4707-16. 2013
    ..We also identified IL-10 as a possible mechanism to explain the lack of influence of inoculum dose on priming of T cells in the lymph node...
  33. ncbi CCR5-deficient mice control Mycobacterium tuberculosis infection despite increased pulmonary lymphocytic infiltration
    Holly M Scott Algood
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    J Immunol 173:3287-96. 2004
    ..Bacterial numbers in the lymph nodes were also higher in CCR5(-/-) mice. Therefore, CCR5 may play a role in the migration of dendritic cells to and from the lymph nodes during M. tuberculosis infection...
  34. pmc Cytotoxicity and secretion of gamma interferon are carried out by distinct CD8 T cells during Mycobacterium tuberculosis infection
    Thorbjorg Einarsdottir
    Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, W1144 Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA 15261, USA
    Infect Immun 77:4621-30. 2009
    ....
  35. ncbi Afferent and efferent interfaces of lymph nodes are distinguished by expression of lymphatic endothelial markers and chemokines
    Amarendra Pegu
    Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA
    Lymphat Res Biol 5:91-103. 2007
    ....
  36. pmc Metronidazole prevents reactivation of latent Mycobacterium tuberculosis infection in macaques
    Philana Ling Lin
    Division of Infectious Diseases, Department of Pediatrics, Children s Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA
    Proc Natl Acad Sci U S A 109:14188-93. 2012
    ..Our data in the nonhuman primate model of active and latent TB supports targeting bacteria in hypoxic environments for preventing reactivation of latent infection and possibly shortening the duration of therapy in active TB...
  37. ncbi CD40, but not CD40L, is required for the optimal priming of T cells and control of aerosol M. tuberculosis infection
    Vanja Lazarevic
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    Immunity 19:823-35. 2003
    ..tuberculosis Hsp70 elicited IL-12 production from WT dendritic cells. This response was absent in both CD40(-/-) dendritic cells and CD40(-/-) mice, suggesting that M. tuberculosis Hsp70 serves as an alternative ligand for CD40 in vivo...
  38. ncbi Chemokines and tuberculosis
    Holly M Scott Algood
    Department of Molecular Genetics and Biochemistry and Molecular Virology and Microbiology Graduate Program, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    Cytokine Growth Factor Rev 14:467-77. 2003
    ..In this review, the current literature on chemokines and M. tuberculosis infection, as well as the specific role that tumor necrosis factor alpha (TNF-alpha) plays in granuloma formation and chemokine expression are discussed...
  39. pmc Aberrant TGF-beta signaling reduces T regulatory cells in ICAM-1-deficient mice, increasing the inflammatory response to Mycobacterium tuberculosis
    Hillarie Plessner Windish
    Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    J Leukoc Biol 86:713-25. 2009
    ..Consequently, the effector T-cell response and inflammation were greater in the lungs of ICAM-1-/- mice, resulting in morbidity due to overwhelming pathology...
  40. pmc Experimental Mycobacterium tuberculosis infection of cynomolgus macaques closely resembles the various manifestations of human M. tuberculosis infection
    Saverio V Capuano
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    Infect Immun 71:5831-44. 2003
    ..In addition, this model will provide an opportunity to study the latent M. tuberculosis infection observed in approximately 90% of all infected humans...
  41. ncbi IL-17 production is dominated by gammadelta T cells rather than CD4 T cells during Mycobacterium tuberculosis infection
    Euan Lockhart
    Department of Molecular Genetics and Biochemistry, Biomedical Science Tower, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    J Immunol 177:4662-9. 2006
    ..tuberculosis-infected dendritic cells. IL-23 is present in the lungs early in infection and the IL-17-producing cells, such as gammadelta T cells, may represent a central innate protective response to pulmonary infection...
  42. pmc Large scale comparison of innate responses to viral and bacterial pathogens in mouse and macaque
    Guy Zinman
    Lane Center for Computational Biology, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America
    PLoS ONE 6:e22401. 2011
    ..On the other hand we also found several species and pathogen specific response patterns. These results provide new insights into mechanisms by which the innate immune system responds to, and interacts with, invading pathogens...
  43. pmc Mycobacterium tuberculosis in chemokine receptor 2-deficient mice: influence of dose on disease progression
    Holly M Scott
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    Infect Immun 70:5946-54. 2002
    ..Functional assays may be necessary to reveal roles for components of the multifactorial immune system...
  44. pmc Understanding latent tuberculosis: a moving target
    Philana Ling Lin
    Department of Pediatrics, Children s Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, PA 15224, USA
    J Immunol 185:15-22. 2010
    ..The immunology of TB is complex and multifaceted. Identifying the immune mechanisms that lead to control of initial infection and prevent reactivation of latent infection is crucial to combating this disease...
  45. pmc HIV-1/mycobacterium tuberculosis coinfection immunology: how does HIV-1 exacerbate tuberculosis?
    Collin R Diedrich
    Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    Infect Immun 79:1407-17. 2011
    ..This review examines the data that support each hypothesis of how HIV manipulates TB pathology while emphasizing a need for more tissue-based experiments...
  46. pmc Latent tuberculosis: what the host "sees"?
    Hannah P Gideon
    Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, W1144 Biomedical Science Tower, Pittsburgh, PA 15261, USA
    Immunol Res 50:202-12. 2011
    ..This review aims to summarize the recent findings in human and non-human primate models of tuberculosis that have led to new concepts of latent tuberculosis...
  47. doi Sterilization of granulomas is common in active and latent tuberculosis despite within-host variability in bacterial killing
    Philana Ling Lin
    1 Department of Pediatrics, Children s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA 2
    Nat Med 20:75-9. 2014
    ..Defining the local factors that dictate outcome will be useful in developing effective interventions to prevent active TB. ..
  48. pmc IFN-γ from CD4 T cells is essential for host survival and enhances CD8 T cell function during Mycobacterium tuberculosis infection
    Angela M Green
    Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    J Immunol 190:270-7. 2013
    ..Thus, although CD4 T cells play additional roles in the control of M. tuberculosis infection, IFN-γ is a major function by which these cells participate in resistance to tuberculosis...
  49. ncbi New insights into mathematical modeling of the immune system
    Penelope A Morel
    Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA
    Immunol Res 36:157-65. 2006
    ..These are collaborative studies between experimental immunologists, mathematicians, and computer scientists...
  50. ncbi Mycobacterial infections and the inflammatory seesaw
    Charles A Scanga
    Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    Cell Host Microbe 7:177-9. 2010
    ..They also demonstrate that polymorphisms in LTA(4)H are associated with susceptibility to mycobacteria in humans...
  51. ncbi Alterations in T lymphocyte profiles of bronchoalveolar lavage fluid from SIV- and Pneumocystis carinii-coinfected rhesus macaques
    Denise A Croix
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    AIDS Res Hum Retroviruses 18:391-401. 2002
    ..These results are similar to immunologic findings in human AIDS-associated PCP and support the usefulness of this model in the study of immune responses to P. carinii...
  52. ncbi Latent tuberculosis: mechanisms of host and bacillus that contribute to persistent infection
    JoAnn M Tufariello
    Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA
    Lancet Infect Dis 3:578-90. 2003
    ..We discuss here current understanding of both host and bacterial factors that contribute to latent and reactivation tuberculosis...
  53. pmc Tuberculous granulomas are hypoxic in guinea pigs, rabbits, and nonhuman primates
    Laura E Via
    Tuberculosis Research Section, Laboratory of Clinical Infectious Disease, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20852, USA
    Infect Immun 76:2333-40. 2008
    ..Thus, three independent lines of evidence support the hypothesis that hypoxic microenvironments are an important feature of some lesions in these animal models of tuberculosis...
  54. pmc Profiling antibodies to Mycobacterium tuberculosis by multiplex microbead suspension arrays for serodiagnosis of tuberculosis
    Imran H Khan
    Center for Comparative Medicine, Department of Pathology and Laboratory Medicine, School of Medicine, University of California, Davis, California 95616, USA
    Clin Vaccine Immunol 15:433-8. 2008
    ..In addition, the MMIA serodetection system has a potential for mining M. tuberculosis open reading frames (about 4,000) to discover novel target proteins for the development of more-comprehensive TB serodiagnostic tests...
  55. pmc Differences in reactivation of tuberculosis induced from anti-TNF treatments are based on bioavailability in granulomatous tissue
    Simeone Marino
    Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA
    PLoS Comput Biol 3:1909-24. 2007
    ..Alternatively, the dose and timing of anti-TNF therapy could be modified. Anti-TNF therapy will likely lead to numerous incidents of primary TB if used in areas where exposure is likely...
  56. pmc The purinergic P2X7 receptor is not required for control of pulmonary Mycobacterium tuberculosis infection
    Amy J Myers
    Department of Medicine, Division of Infectous Disease, BRB 1029, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106 4984, USA
    Infect Immun 73:3192-5. 2005
    ..P2X7(-/-) mice controlled infection in lungs as well as wild-type mice, suggesting that the P2X7 receptor is not required for control of pulmonary M. tuberculosis infection...
  57. ncbi Mutual attraction: does it benefit the host or the bug?
    JoAnne L Flynn
    Nat Immunol 5:778-9. 2004
  58. ncbi Dendritic cell trafficking and antigen presentation in the human immune response to Mycobacterium tuberculosis
    Simeone Marino
    Department of Microbiology and Immunology, University of Michigan Medical School, 6730 Medical Science Building II, Ann Arbor, MI 48109, USA
    J Immunol 173:494-506. 2004
    ..This will induce the most protective T cell response...
  59. ncbi Structural-functional relationships of TNF-alpha antagonists: next steps
    Frank J Dann
    Amgen Inc, Thousand Oaks, California 91320 1799, USA
    J Investig Dermatol Symp Proc 12:46-7. 2007
    ..The data presented in this supplement highlight the need for further research into these key areas, and illustrate our current understanding of the mode of action of TNF blockers as only the tip of the iceberg...
  60. ncbi New approaches to tuberculosis surveillance in nonhuman primates
    Nicholas W Lerche
    Pathogen Detection Laboratory, California National Primate Research Center, University of California, Davis, CA 95616, USA
    ILAR J 49:170-8. 2008
    ..In this article we describe the characteristics of these newer screening tests and discuss their potential contributions to NHP tuberculosis surveillance programs...
  61. ncbi Contribution of CD8+ T cells to control of Mycobacterium tuberculosis infection
    Dhruv Sud
    Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, 48109, USA
    J Immunol 176:4296-314. 2006
    ..We also determined the minimum levels of effector memory cells of each T cell subset (CD4(+) and CD8(+)) in providing effective protection following vaccination...

Research Grants38

  1. A NON-HUMAN PRIMATE MODEL OF TUBERCULOSIS AND AIDS
    Joanne Flynn; Fiscal Year: 2004
    ..Once a non-human primate model for tuberculosis is established, it could be used to test vaccines, immunotherapy, and new treatment options for tuberculosis. ..
  2. CD4 T Cells in Tuberculosis
    Joanne Flynn; Fiscal Year: 2006
    ..The results obtained are relevant to vaccine design and efficacy, as well as to understanding treatment and prevention of tuberculosis in HIV+ (and therefore CD4 T cell deficient) individuals. ..
  3. FUNCTION OF CD8 T CELLS IN TUBERCULOSIS
    Joanne Flynn; Fiscal Year: 2006
    ..abstract_text> ..
  4. Immunology of Infectious Disease
    Joanne Flynn; Fiscal Year: 2007
    ....
  5. Latent and Reactivation Tuberculosis
    Joanne Flynn; Fiscal Year: 2007
    ..These studies are the first to study reactivation in an immunologically tractable animal model that is similar to human latent tuberculosis. ..
  6. FUNCTION OF CD8 T CELLS IN TUBERCULOSIS
    Joanne Flynn; Fiscal Year: 2009
    ..Determine whether CD8 T cell memory is initiated, maintained and recalled in the setting of cured or latent tuberculosis, and the factors that contribute to the ineffective memory response. ..
  7. CD4 T Cells in Tuberculosis
    JoAnne L Flynn; Fiscal Year: 2010
    ..This application will address how CD4 T cells contribute to immunity to tuberculosis, and provide insight into improving the CD4 T cell response, and possibly improving vaccines against this disease. ..
  8. FUNCTION OF CD8 T CELLS IN TUBERCULOSIS
    JoAnne L Flynn; Fiscal Year: 2010
    ..Determine whether CD8 T cell memory is initiated, maintained and recalled in the setting of cured or latent tuberculosis, and the factors that contribute to the ineffective memory response. ..
  9. CD4 T Cells in Tuberculosis
    JoAnne L Flynn; Fiscal Year: 2011
    ..This application will address how CD4 T cells contribute to immunity to tuberculosis, and provide insight into improving the CD4 T cell response, and possibly improving vaccines against this disease. ..
  10. FUNCTION OF CD8T CELLS IN TUBERCULOSIS
    Joanne Flynn; Fiscal Year: 2001
    ....
  11. Pathogen-Host Standoff: Persistent and Latent Infection
    Joanne Flynn; Fiscal Year: 2004
    ..This meeting seeks to bring together researchers from a variety of fields, with the common goal of understanding how persistent pathogens survive and how the host responds to such pathogens. ..
  12. Defining how the spectrum of latency affects reactivation of TB
    Denise E Kirschner; Fiscal Year: 2010
    ..Here we integrate data from humans and animal models with computational and mathematical models in a comprehensive systems biology approach to a better understanding of latent TB and the factors that lead to reactivation. ..