Cellular Immunity Against Ehrlichia chaffeensis

Summary

Principal Investigator: ROMAN GANTA
Abstract: Human ehrlichiosis is caused by three agents including Ehrlichia chaffeensis, Anaplasma phagocytophila and by E. ewengii. These potentially fatal infections pose a serious threat to public health, particularly to immunocompromised and elderly people. However, little is known about the mechanisms of host resistance and reasons for the emergence of these diseases. This project proposes to characterize the host immune response necessary for clearance using mouse as the experimental host because the course of E. chaffeensis infection is similar between immunocompetent humans and mice and the model will provide data for human applications. Moreover, the extensive array of molecular, immunological and genetic tools available for mice will allow us to manipulate the system in ways that are not possible in other species. Specifically, three hypotheses will be tested: 1)TH1 type helper T-cells are required for clearance of E. chaffeensis; 2) Secreted cytokines from T-cells are needed for host resistance to E. chaffeensis infections; 3) Macrophage activation contributes to the clearance of E. chaffeensis. Several observations form the basis for this project: immunocompetent mice clear E. chaffeensis by 16 days and the clearance is associated with the expression of an E. chaffeensis-specific TH1 type IgG response, CTL response and granuloma formation; the infections are fatal in SCID mice lacking T- and B-cells; mice lacking functional MHCII genes establish long-term persistent infections after E. chaffeensis challenge; mice deficient for macrophage activation develop short-term persistent infections; and prior activation with IFN-gamma inhibits monocyte infections with E. chaffeensis. The importance of helper T-cells, cytotoxic T-cells, B-cell responses, cytokines, and macrophage activation will be evaluated using several mouse strains with different genetic backgrounds and by manipulating their immune systems to diminish or enhance particular immune components. Infections will be monitored using bacteriological, molecular, immunological, and pathological analyses to assess host immunity and infection status. The long-term goals of this project are to elucidate host immune mechanisms, pathogen evasion strategies and to ultimately use the information to devise effective intervention measures against E. chaffeensis and other closely related organisms.
Funding Period: 2003-09-30 - 2009-01-31
more information: NIH RePORT

Top Publications

  1. pmc Evaluation of in vitro macrophage differentiation during space flight
    M Teresa Ortega
    Division of Biology, Kansas State University, Manhattan, KS 66506, USA
    Adv Space Res 49:1441-1455. 2012
  2. pmc Ehrlichia chaffeensis replication sites in adult Drosophila melanogaster
    Rishi Drolia
    Division of Biology, Kansas State University, Manhattan, KS 66506, USA
    Int J Med Microbiol 303:40-9. 2013
  3. pmc Identification of critical host mitochondrion-associated genes during Ehrlichia chaffeensis infections
    Tonia Von Ohlen
    Kansas State University, Division of Biology, Manhattan, Kansas, USA
    Infect Immun 80:3576-86. 2012
  4. pmc Interactive changes between macrophages and adipocytes
    Linglin Xie
    Division of Biology, Kansas State University, Manhattan, KS 66506, USA
    Clin Vaccine Immunol 17:651-9. 2010
  5. pmc Male CD81 knockout genotype disrupts Mendelian distribution of offspring
    Whitney J Mordica
    Division of Biology, Kansas State University, Manhattan, Kansas, USA
    Comp Med 60:196-9. 2010
  6. pmc Evaluation of macrophage plasticity in brown and white adipose tissue
    M Teresa Ortega
    Division of Biology, Kansas State University, Manhattan, KS 66506 4901, USA
    Cell Immunol 271:124-33. 2011
  7. pmc Ehrlichia chaffeensis infections in Drosophila melanogaster
    Alison Luce-Fedrow
    Kansas State University, Division of Biology, 116 Ackert Hall, Manhattan, KS 66506, USA
    Infect Immun 77:4815-26. 2009
  8. pmc Promoter analysis of macrophage- and tick cell-specific differentially expressed Ehrlichia chaffeensis p28-Omp genes
    Lalitha Peddireddi
    Department of Diagnostic Medicine Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA
    BMC Microbiol 9:99. 2009
  9. pmc Mutation of juxtamembrane cysteines in the tetraspanin CD81 affects palmitoylation and alters interaction with other proteins at the cell surface
    Caroline Delandre
    Molecular, Cellular and Developmental Biology Program, Kansas State University, Manhattan, KS 66506, USA
    Exp Cell Res 315:1953-63. 2009
  10. ncbi Molecular characterization of Ehrlichia interactions with tick cells and macrophages
    Roman Reddy Ganta
    Department of Diagnostic Medicine Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA
    Front Biosci (Landmark Ed) 14:3259-73. 2009

Scientific Experts

  • Roman Reddy Ganta
  • Lalitha Peddireddi
  • Olivier Silvie
  • Stephen K Chapes
  • M Teresa Ortega
  • Chuanmin Cheng
  • Tonia Von Ohlen
  • Alison Luce-Fedrow
  • Whitney J Mordica
  • Betsey E Potts
  • Kamesh R Sirigireddy
  • Vijayakrishna Singu
  • Linglin Xie
  • Rishi Drolia
  • Silvia Mora
  • Rollie J Clem
  • A Lorena Passarelli
  • Caroline Delandre
  • Gwi Moon Seo
  • Derek A Mosier
  • Stephen Keith Chapes
  • Laura J Armbrust
  • Nanyan Lu
  • Ryan J Gallagher
  • Jenna L Kennedy
  • Keith M Woods
  • Taryn R Penabaz
  • Louis S Stodieck
  • Daila S Gridley
  • Michael J Pecaut
  • Virginia Ferguson
  • Marcia L Hart
  • Laura L Snyder
  • John Tomich
  • Dan Boyle
  • Daniel Boyle
  • Ulrike Munderloh
  • Marcy L Hart
  • Ethany L Nelson
  • Haijie Liu
  • S K Chapers

Detail Information

Publications28

  1. pmc Evaluation of in vitro macrophage differentiation during space flight
    M Teresa Ortega
    Division of Biology, Kansas State University, Manhattan, KS 66506, USA
    Adv Space Res 49:1441-1455. 2012
    ..There also was a surprising pattern of space flight influence on genes of the coagulation pathway. These data confirm that a space flight can have an impact on the in vitro development of macrophages from mouse bone marrow cells...
  2. pmc Ehrlichia chaffeensis replication sites in adult Drosophila melanogaster
    Rishi Drolia
    Division of Biology, Kansas State University, Manhattan, KS 66506, USA
    Int J Med Microbiol 303:40-9. 2013
    ..Our data suggest that in Drosophila, E. chaffeensis replicates within the hemocytes, the insect homolog of mammalian macrophages, and in the fat body, the liver homolog of mammals...
  3. pmc Identification of critical host mitochondrion-associated genes during Ehrlichia chaffeensis infections
    Tonia Von Ohlen
    Kansas State University, Division of Biology, Manhattan, Kansas, USA
    Infect Immun 80:3576-86. 2012
    ..chaffeensis replication and that it may be important for the provision of CTP, uridine, and cytidine nucleotides...
  4. pmc Interactive changes between macrophages and adipocytes
    Linglin Xie
    Division of Biology, Kansas State University, Manhattan, KS 66506, USA
    Clin Vaccine Immunol 17:651-9. 2010
    ....
  5. pmc Male CD81 knockout genotype disrupts Mendelian distribution of offspring
    Whitney J Mordica
    Division of Biology, Kansas State University, Manhattan, Kansas, USA
    Comp Med 60:196-9. 2010
    ..Sex distribution did not differ among pups sired by CD81(null/null) compared with CD81(+/null) mice. The data suggest that the effect of the CD81(null/null) paternal genotype on offspring is manifested early in development or in utero...
  6. pmc Evaluation of macrophage plasticity in brown and white adipose tissue
    M Teresa Ortega
    Division of Biology, Kansas State University, Manhattan, KS 66506 4901, USA
    Cell Immunol 271:124-33. 2011
    ..These data suggest that the C2D macrophage phenotype can change rapidly and distinct phenotypes are induced by different microenvironments...
  7. pmc Ehrlichia chaffeensis infections in Drosophila melanogaster
    Alison Luce-Fedrow
    Kansas State University, Division of Biology, 116 Ackert Hall, Manhattan, KS 66506, USA
    Infect Immun 77:4815-26. 2009
    ..chaffeensis suggests that D. melanogaster is a suitable host for E. chaffeensis. In the future, it will be a useful tool to unlock some of the in vivo mysteries of this arthropod-borne bacterium...
  8. pmc Promoter analysis of macrophage- and tick cell-specific differentially expressed Ehrlichia chaffeensis p28-Omp genes
    Lalitha Peddireddi
    Department of Diagnostic Medicine Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA
    BMC Microbiol 9:99. 2009
    ..We also demonstrated that host response differs considerably for macrophage and tick cell-derived bacteria with delayed clearance of the pathogen originating from tick cells...
  9. pmc Mutation of juxtamembrane cysteines in the tetraspanin CD81 affects palmitoylation and alters interaction with other proteins at the cell surface
    Caroline Delandre
    Molecular, Cellular and Developmental Biology Program, Kansas State University, Manhattan, KS 66506, USA
    Exp Cell Res 315:1953-63. 2009
    ....
  10. ncbi Molecular characterization of Ehrlichia interactions with tick cells and macrophages
    Roman Reddy Ganta
    Department of Diagnostic Medicine Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA
    Front Biosci (Landmark Ed) 14:3259-73. 2009
    ..This review presents the current understanding of tick-Ehrlichia interactions and implications for future...
  11. pmc Macrophage cell lines use CD81 in cell growth regulation
    Whitney J Mordica
    Division of Biology, Kansas State University, 116 Ackert Hall, Manhattan, KS 66506 4901, USA
    In Vitro Cell Dev Biol Anim 45:213-25. 2009
    ..These data suggest that CD81 potentially plays a role in macrophage cell line growth regulation...
  12. pmc Shifts in bone marrow cell phenotypes caused by spaceflight
    M Teresa Ortega
    Kansas State University, Manhattan, Kansas, USA
    J Appl Physiol (1985) 106:548-55. 2009
    ..However, the reduction in less differentiated cells may forebode future consequences for macrophage production and host defenses. This is of particular importance to considerations of future long-term spaceflights...
  13. pmc Defining the immune response to Ehrlichia species using murine models
    Stephen K Chapes
    Division of Biology, College of Arts and Sciences, Kansas State University, Manhattan, KS 66506, USA
    Vet Parasitol 158:344-59. 2008
    ..In this paper, we provide our perspective of the current understanding of the immune response against E. chaffeensis in relation to other related Anaplasmataceae pathogens...
  14. pmc Multiplex detection of Ehrlichia and Anaplasma species pathogens in peripheral blood by real-time reverse transcriptase-polymerase chain reaction
    Kamesh R Sirigireddy
    Department of Diagnostic Medicine Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Ave, Manhattan, Kansas 66506, USA
    J Mol Diagn 7:308-16. 2005
    ..platys and co-infection with E. canis and A. platys. The multipathogen detection and novel positive control development procedures described here will be valuable in monitoring infections in people, other vertebrates, and ticks...
  15. ncbi Correlation of results of pulmonary computed tomography and pathologic findings in mice with Pasteurella-induced pneumonia
    Laura J Armbrust
    Department of Clinical Sciences College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA
    Am J Vet Res 66:835-8. 2005
    ..To determine correlation between results of computed tomography (CT) versus pathologic examination for determining the volume percentage of affected lung in mice experimentally infected with Pasteurella pneumotropica...
  16. ncbi Mouse infection models for space flight immunology
    Stephen Keith Chapes
    Division of Biology and Department of Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, KS 66506, USA
    Adv Space Biol Med 10:81-104. 2005
    ..We propose that some of these experimental challenge models will be useful to assess the effects of space flight on host resistance to infection...
  17. ncbi Cholesterol contributes to the organization of tetraspanin-enriched microdomains and to CD81-dependent infection by malaria sporozoites
    Olivier Silvie
    INSERM, U511, 91 Bd de l Hopital, F 75013 Paris, France
    J Cell Sci 119:1992-2002. 2006
    ....
  18. ncbi Unique macrophage and tick cell-specific protein expression from the p28/p30-outer membrane protein multigene locus in Ehrlichia chaffeensis and Ehrlichia canis
    Vijayakrishna Singu
    Department of Diagnostic Medicine Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, 66506, USA
    Cell Microbiol 8:1475-87. 2006
    ..Differential expression of proteins within the p28/p30-Omp locus may therefore be vital for adaptation of Ehrlichia species to their dual host life cycle...
  19. pmc Differential clearance and immune responses to tick cell-derived versus macrophage culture-derived Ehrlichia chaffeensis in mice
    Roman R Ganta
    Department of Diagnostic Medicine Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Ave, Manhattan, KS 66506, USA
    Infect Immun 75:135-45. 2007
    ..These data suggest that the host response to E. chaffeensis depends on the source of the bacteria and that this experimental model requires the most natural inoculum possible to allow for a realistic understanding of host resistance...
  20. ncbi Functions of C2D macrophage cells after adoptive transfer
    Betsey E Potts
    Division of Biology, Kansas State University, Manhattan, KS 66506, USA
    J Leukoc Biol 83:602-9. 2008
    ..These data indicate that C2D macrophage cells exhibit distinct functions because of in vivo signals that are absent during in vitro culture...
  21. pmc Differentiation of C2D macrophage cells after adoptive transfer
    Betsey E Potts
    Division of Biology, Department of Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, Kansas 66506, USA
    Clin Vaccine Immunol 15:243-52. 2008
    ..These responses were independent of the genetic backgrounds of the recipient mice. These data support the hypothesis and indicate that C2D macrophage cells respond to in vivo signals that are absent during in vitro culture...
  22. pmc Use of Drosophila S2 cells as a model for studying Ehrlichia chaffeensis infections
    Alison Luce-Fedrow
    Kansas State University, Division of Biology, Manhattan, KS 66506, USA
    Appl Environ Microbiol 74:1886-91. 2008
    ..chaffeensis. The use of a Drosophila system has the potential to serve as a model system for studying Ehrlichia due to its completed genome, ease of genetic manipulation, and the availability of mutants...
  23. pmc Total, membrane, and immunogenic proteomes of macrophage- and tick cell-derived Ehrlichia chaffeensis evaluated by liquid chromatography-tandem mass spectrometry and MALDI-TOF methods
    Gwi Moon Seo
    Department of Diagnostic Medicine Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Avenue, Manhattan, KS 66506, USA
    Infect Immun 76:4823-32. 2008
    ....
  24. ncbi Laboratory maintenance of Ehrlichia chaffeensis and Ehrlichia canis and recovery of organisms for molecular biology and proteomics studies
    Chuanmin Cheng
    Department of Diagnostic Medicine Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas, USA
    Curr Protoc Microbiol . 2008
    ..The unit also includes methods useful in purifying bacteria from the host cells and to evaluate proteins by 2-D gel electrophoresis and western blotting...
  25. ncbi Isolation and molecular detection of Ehrlichia from vertebrate animals
    Chuanmin Cheng
    Department of Diagnostic Medicine Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas, USA
    Curr Protoc Microbiol . 2008
    ..chaffeensis and E. canis from infected blood samples collected from dogs, deer, and human patients are described. PCR and RT-PCR methods for sensitive detection of Ehrlichia infection are also discussed...
  26. pmc Ehrlichia chaffeensis expresses macrophage- and tick cell-specific 28-kilodalton outer membrane proteins
    Vijayakrishna Singu
    Department of Diagnostic Medicine Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Ave, Manhattan, KS 66506, USA
    Infect Immun 73:79-87. 2005
    ..Host cell-specific protein expression coupled with posttranslational modifications may be a hallmark for the pathogen's adaptation to a dual-host life cycle and its persistence...