Genomes and Genes
Affiliation: Harvard University
- TLR2 mediates recognition of live Staphylococcus epidermidis and clearance of bacteremiaTobias Strunk
School of Paediatrics and Child Health, University of Western Australia, Perth, Australia
PLoS ONE 5:e10111. 2010..The role of TLR2 in responses of primary blood leukocytes to live SE and in clearance of SE bacteremia, the most common clinical manifestation of SE infection, is unknown...
- Neonatal host defense against Staphylococcal infectionsMelanie R Power Coombs
Pathology, Dalhousie University, Halifax, NS, Canada
Clin Dev Immunol 2013:826303. 2013..Characterization of distinct aspects of the neonatal immune response is defining novel approaches to enhance host defense to prevent and/or treat staphylococcal infection in this vulnerable population. ..
- A neonatal model of intravenous Staphylococcus epidermidis infection in mice <24 h old enables characterization of early innate immune responsesKenny D Kronforst
Newborn Medicine, Boston Children s Hospital, Boston, Massachusetts, United States of America
PLoS ONE 7:e43897. 2012..This novel model can now be used to characterize immune ontogeny, evaluate infection biomarkers, and assess preventative and therapeutic modalities...
- Immune response to vaccine adjuvants during the first year of lifeOfer Levy
Boston Children s Hospital and Harvard Medical School, Boston, MA, USA
Vaccine 31:2500-5. 2013..Herein, we discuss the potential implications of innate immune ontogeny for the activity of adjuvants contained in licensed infant vaccines, as well as future directions for rational design of adjuvanted vaccines for this age group...
- The adenosine system selectively inhibits TLR-mediated TNF-alpha production in the human newbornOfer Levy
Infectious Diseases, Children s Hospital, Boston, MA 02115, USA
J Immunol 177:1956-66. 2006..We conclude that the distinct adenosine system of newborns polarizes TLR-mediated cytokine production during the perinatal period and may thereby modulate their innate and adaptive immune responses...
- Unique efficacy of Toll-like receptor 8 agonists in activating human neonatal antigen-presenting cellsOfer Levy
Division of Infectious Diseases, Children s Hospital Boston, Boston, MA 02115, USA
Blood 108:1284-90. 2006..We conclude that TLR8 agonists are uniquely efficacious in activating costimulatory responses in neonatal APCs and suggest that these agents are promising candidate adjuvants for enhancing immune responses in human newborns...
- Development of newborn and infant vaccinesGuzman Sanchez-Schmitz
Children s Hospital Boston, Boston, MA 02115, USA
Sci Transl Med 3:90ps27. 2011..Therefore, understanding and modeling age-specific human immune responses will be vital to the rational design and development of safe and effective vaccines for newborns and infants...
- Selective impairment of TLR-mediated innate immunity in human newborns: neonatal blood plasma reduces monocyte TNF-alpha induction by bacterial lipopeptides, lipopolysaccharide, and imiquimod, but preserves the response to R-848Ofer Levy
Channing Laboratory, Brigham and Women s Hospital, Boston, MA 02115, USA
J Immunol 173:4627-34. 2004..Conversely, relative preservation of responses to R-848 may present unique opportunities for augmenting innate and acquired immunity in the human newborn...
- Innate immunity of the human newborn: distinct cytokine responses to LPS and other Toll-like receptor agonistsOfer Levy
Division of Infectious Diseases, Children s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
J Endotoxin Res 11:113-6. 2005..Definition of the mechanisms underlying distinct neonatal immunity promises to identify novel ways to prevent and treat infection in this relatively high-risk population...
- Innate immunity of the newborn: basic mechanisms and clinical correlatesOfer Levy
Department of Medicine, Division of Infectious Diseases, Children s Hospital Boston and Harvard Medical School, Boston, MA 02115, USA
Nat Rev Immunol 7:379-90. 2007..This Review describes innate immunity in newborns and discusses how this knowledge might be used to prevent and treat infection in this vulnerable population...
- Responsiveness of human monocytes to the commensal bacterium Staphylococcus epidermidis develops late in gestationTobias Strunk
University of Western Australia Centre for Neonatal Research and Education, Perth, Western Australia, Australia
Pediatr Res 72:10-8. 2012..We hypothesized that the innate immune responses to SE in preterm infants are impaired in a gestational age (GA)-dependent manner...
- Bactericidal/permeability-increasing protein (rBPI21) and fluoroquinolone mitigate radiation-induced bone marrow aplasia and deathEva C Guinan
Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, MA 02215, USA
Sci Transl Med 3:110ra118. 2011....
- Innate immune activation in neonatal tracheal aspirates suggests endotoxin-driven inflammationKatheryn E Nathe
Department of Medicine, Children s Hospital Boston, Massachusetts, USA
Pediatr Res 72:203-11. 2012..We characterized innate immune activation in TAs of mechanically ventilated neonates...
- The ultra-potent and selective TLR8 agonist VTX-294 activates human newborn and adult leukocytesDavid J Dowling
Department of Medicine, Division of Infectious Diseases, Boston Children s Hospital, Boston, Massachusetts, USA
PLoS ONE 8:e58164. 2013..Effects of VTX-294 and R-848 in combination with monophosphoryl lipid A (MPLA; TLR4) were also assessed...
- Neonatal immune responses to coagulase-negative staphylococciTobias Strunk
School of Paediatrics and Child Health, University of Western Australia, Perth, Australia
Curr Opin Infect Dis 20:370-5. 2007..This review summarizes current knowledge on the human immune response to coagulase-negative staphylococci, with particular emphasis on the neonatal innate immune system...
- Deficient expression of bactericidal/permeability-increasing protein in immunocompromised hosts: translational potential of replacement therapyChristine D Palmer
Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
Biochem Soc Trans 39:994-9. 2011....
- Imidazoquinoline Toll-like receptor 8 agonists activate human newborn monocytes and dendritic cells through adenosine-refractory and caspase-1-dependent pathwaysVictoria J Philbin
Department of Medicine, Division of Infectious Diseases, Children s Hospital Boston, Boston, Mass Harvard Medical School, Boston, MA 02115, USA
J Allergy Clin Immunol 130:195-204.e9. 2012....
- Identification of single nucleotide polymorphisms in hematopoietic cell transplant patients affecting early recognition of, and response to, endotoxinEva C Guinan
Boston Children s Hospital, Boston, MA, USA Harvard Medical School, Boston, MA, USA Dana Farber Cancer Institute, Boston, MA, USA
Innate Immun 20:697-711. 2014..These findings suggest that specific LBP, CD14 and BPI SNPs might be contributory assessments in studies where clinical outcome may be affected by host response to endotoxin and bacterial infection. ..
- Method of bacterial killing differentially affects the human innate immune response to Staphylococcus epidermidisTobias Strunk
School of Paediatrics and Child Health, University of Western Australia, Subiaco
Innate Immun 17:508-16. 2011..The effects of the bacterial preparation method on the activation of innate signalling pathways by the common opportunistic pathogen Staphylococcus epidermidis (SE) are unknown...
- Critical role of the complement system in group B streptococcus-induced tumor necrosis factor alpha releaseOfer Levy
Division of Infectious Diseases, Children s Hospital, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
Infect Immun 71:6344-53. 2003....
- Antimicrobial proteins and peptides: anti-infective molecules of mammalian leukocytesOfer Levy
Department of Medicine, Division of Infectious Diseases, Children s Hospital, Harvard Medical School, Boston, Massachusetts, USA
J Leukoc Biol 76:909-25. 2004..From a clinical perspective, congeners of several of the APP have been developed as potential therapeutic agents and have entered clinical trials with some evidence of benefit...
- Novel vaccines: bridging research, development and productionAlicia Demirjian
Department of Medicine, Division of Infectious Diseases, Children s Hospital, Boston, MA 02115, USA
Expert Rev Vaccines 7:1321-4. 2008....
- Recombinant bactericidal/permeability-increasing protein rBPI21 protects against pneumococcal diseaseAmit Srivastava
Division of Infectious Diseases, Department of Medicine, Children s Hospital, Boston, MA 02115, USA
Infect Immun 75:342-9. 2007..We have thus discovered a novel interaction between pneumococcus and rBPI21, a potent antimicrobial peptide previously considered to target only gram-negative bacteria...
- The effect of stable macromolecular complexes of ionic polyphosphazene on HIV Gag antigen and on activation of human dendritic cells and presentation to T-cellsChristine D Palmer
Boston Children s Hospital, Boston, MA, USA Harvard Medical School, Boston, MA, USA
Biomaterials 35:8876-86. 2014..Moreover, polyphosphazenes can further reduce cost of vaccine production and distribution through their dose-sparing and antigen-stabilizing properties, thus potentially eliminating the need for cold chain distribution. ..
- 17(R)-Resolvin D1 differentially regulates TLR4-mediated responses of primary human macrophages to purified LPS and live E. coliChristine D Palmer
Children s Hospital Boston, Boston, MA 02115, USA
J Leukoc Biol 90:459-70. 2011..coli in an LPS- and TLR4-dependent manner, such that this Rv could promote resolution of GNB/LPS-driven inflammation by reducing m proinflammatory responses to isolated LPS and increasing m responses important for clearance of infection...
- Endotoxin-directed innate immunity in tracheal aspirates of mechanically ventilated human neonatesKatheryn E Nathe
Department of Medicine, Children s Hospital Boston, Boston, Massachusetts 02115, USA
Pediatr Res 66:191-6. 2009..TA extracellular BPI, LBP, and sCD14 were positively correlated. TAs from intubated neonates demonstrate endotoxin accumulation and mobilization of endotoxin-directed innate immunity, potentially contributing to pulmonary inflammation...
- Allogeneic transplantation successfully corrects immune defects, but not susceptibility to colitis, in a patient with nuclear factor-kappaB essential modulator deficiencySung Yun Pai
Division of Hematology Oncology, Children s Hospital Boston, Boston, MA 02115, USA
J Allergy Clin Immunol 122:1113-1118.e1. 2008..Boys with X-linked ectodermal dysplasia and immunodeficiency caused by mutations of nuclear factor-kappaB essential modulator have defects in innate and adaptive immunity, and some have colitis...
- Therapeutic potential of the bactericidal/permeability-increasing proteinOfer Levy
Division of Infectious Diseases, Children s Hospital of Boston, MA, USA
Expert Opin Investig Drugs 11:159-67. 2002..Identification and evaluation of additional disease entities characterised by Gram-negative bacteraemia and/or endotoxaemia as possible targets for BPI therapy continues...
- Neonatal babesiosis: case report and review of the literatureLeanne M Fox
Division of Infectious Diseases, Children s Hospital Boston, Harvard Medical School, Boston, MA
Pediatr Infect Dis J 25:169-73. 2006..Of neonatal babesiosis reported in the literature, 9 other cases are reviewed, including 6 that were transfusion-associated, 2 congenital and 2 tick transmitted...
- Adenosine modulates Toll-like receptor function: basic mechanisms and translational opportunitiesMelanie R Power Coombs
Department of Medicine Infectious Diseases, Children s Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA
Expert Rev Anti Infect Ther 9:261-9. 2011..Adenosine analogs are used clinically to treat arrhythmias and apnea of prematurity. Herein, we consider the potential of adenosine analogs as innate immune response modifiers to prevent and/or treat infection...
- Genetic screening for susceptibility to infection in the NICU settingOfer Levy
Division of Infectious Diseases, Children s Hospital, Boston, Massachusetts 02115, USA
Pediatr Res 55:546-8. 2004
- Functional and biochemical characterization of epithelial bactericidal/permeability-increasing proteinGeraldine Canny
Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
Am J Physiol Gastrointest Liver Physiol 290:G557-67. 2006..Taken together, these data confirm the transcriptional regulation of BPI in intestinal epithelia and provide insight into the relevance of BPI as an anti-infective molecule at intestinal surfaces...
- Safety and efficacy of neonatal vaccinationAlicia Demirjian
Department of Medicine, Division of Infectious Diseases, Children s Hospital Boston, Boston, MA 02115, USA
Eur J Immunol 39:36-46. 2009..This review focuses on safety and efficacy of neonatal vaccination in humans as well as recent research employing novel approaches to enhance the efficacy of neonatal vaccination...
- Neutrophil defense in patients undergoing bone marrow transplantation: bactericidal/permeability-increasing protein (BPI) and defensins in graft-derived neutrophilsOfer Levy
Division of Infectious Diseases, General Clinical Research Center, and Medicine, Children s Hospital, Boston, Massachusetts, USA
Transplantation 73:1522-6. 2002..To assess potential qualitative defects in neutrophil function in patients undergoing BMT, we measured neutrophil content of the antimicrobial (poly)peptides BPI and defensins...
- Impaired innate immunity at birth: deficiency of bactericidal/permeability-increasing protein (BPI) in the neutrophils of newbornsOfer Levy
Division of Infectious Diseases, Children s Hospital and Channing Research Laboratory, Brigham and Women s Hospital, 181 Longwood Avenue, Boston, MA 02115, USA
Pediatr Res 51:667-9. 2002
- Soluble ecto-5'-nucleotidase (5'-NT), alkaline phosphatase, and adenosine deaminase (ADA1) activities in neonatal blood favor elevated extracellular adenosineMatthew Pettengill
From the Department of Medicine, Division of Infectious Diseases, Boston Children s Hospital, Boston, Massachusetts 02115
J Biol Chem 288:27315-26. 2013..Targeted manipulation of purine-metabolizing enzymes may benefit this vulnerable population. ..
- Ontogeny of early life immunityDavid J Dowling
Department of Medicine, Division of Infectious Diseases, Boston Children s Hospital, Boston, MA, USA Harvard Medical School, Boston, MA, USA
Trends Immunol 35:299-310. 2014....
- Disseminated varicella infection due to the vaccine strain of varicella-zoster virus, in a patient with a novel deficiency in natural killer T cellsOfer Levy
Division Infectious Diseases, Children s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
J Infect Dis 188:948-53. 2003....
- Endotoxemia and elevation of lipopolysaccharide-binding protein after hematopoietic stem cell transplantationOfer Levy
Dicision of Infectious Diseases, The Children s Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA
Pediatr Infect Dis J 22:978-81. 2003..Our aim was to gain insight into the potential role of endotoxin and endotoxin-induced acute phase proteins in children undergoing SCT...
- Developmental biology of the innate immune response: implications for neonatal and infant vaccine developmentVictoria Jane Philbin
Department of Medicine, Children s Hospital Boston and Harvard Medical School, Boston, Massachusetts 02115, USA
Pediatr Res 65:98R-105R. 2009..This review summarizes recent developments in the field of innate immunity emphasizing developmental expression in the fetus, newborn, and infant and its implications for the design of more effective neonatal and infant vaccines...
- Innate immunity of the human newborn is polarized toward a high ratio of IL-6/TNF-alpha production in vitro and in vivoDonatella F Angelone
Catholic University of the Sacred Heart, Rome, Italy
Pediatr Res 60:205-9. 2006..A high ratio of stimulus-induced IL-6/TNF-alpha production is likely to profoundly modulate both innate and adaptive immune responses in the human newborn...
- Defective innate immunity predisposes murine neonates to poor sepsis outcome but is reversed by TLR agonistsJames L Wynn
Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610 0286, USA
Blood 112:1750-8. 2008..These benefits were independent of the adaptive immune system and type I interferon signaling. Improving innate immune function with select TLR agonists may be a useful strategy to prevent neonatal sepsis mortality...
- Human nuclear factor kappa B essential modulator mutation can result in immunodeficiency without ectodermal dysplasiaJordan S Orange
Division of Immunology, Children s Hospital of Philadelphia, PA, USA
J Allergy Clin Immunol 114:650-6. 2004..Male subjects with these mutant NEMO molecules have an X-linked syndrome known as ectodermal dysplasia with immunodeficiency, which is characterized by severe infections, with herpesviruses, bacteria, and mycobacterial susceptibility...
- Selective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunityCheng Lung Ku
Laboratory of Human Genetics of Infectious Diseases, U550, Institut National de la Sante et de la Recherche Medicale, 75015 Paris, France
J Exp Med 204:2407-22. 2007..Conversely, IRAK-4-dependent human TLRs appear to play a redundant role in protective immunity to most infections, at most limited to childhood immunity to some pyogenic bacteria...
- Evidence of a bactericidal permeability increasing protein in an invertebrate, the Crassostrea gigas Cg-BPIMarcelo Gonzalez
IFREMER, Centre National de la Recherche Scientifique, Universite Montpellier 2, Unité Mixte de Recherche 5119, Ecosystèmes Lagunaires, Place E Bataillon, CC80, 34095 Montpellier Cedex 5, France
Proc Natl Acad Sci U S A 104:17759-64. 2007..To our knowledge, this is the first characterization of a BPI in an invertebrate...
- Lipid mediator-induced expression of bactericidal/ permeability-increasing protein (BPI) in human mucosal epitheliaGeraldine Canny
Department of Veterinary Physiology, University College of Dublin, Dublin 4, Ireland
Proc Natl Acad Sci U S A 99:3902-7. 2002..These studies identify a previously unappreciated "molecular shield" for protection of mucosal surfaces against Gram-negative bacteria and their endotoxin...
- Complexes of HLA-G protein on the cell surface are important for leukocyte Ig-like receptor-1 functionTsufit Gonen-Gross
Lautenberg Center for General and Tumor Immunology, Hebrew University Hadassah Medical School, Jerusalem, Israel
J Immunol 171:1343-51. 2003..These oligomers, unique among the class I MHC proteins, probably bind to LIR-1 with increased avidity, resulting in an enhanced inhibitory function of LIR-1 and an impaired killing function of NK cells...
- TCR zeta down-regulation under chronic inflammation is mediated by myeloid suppressor cells differentially distributed between various lymphatic organsAnalía V Ezernitchi
The Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel
J Immunol 177:4763-72. 2006..Such an environment is anticipated to limit the success of immunotherapeutic strategies based on vaccination and T cell transfer, which are currently under investigation for immunotherapy of cancer...
- Determinants of Innate Immunity to Group B StreptococciOfer Levy; Fiscal Year: 2005..abstract_text> ..
- Adenosine Shapes Neonatal Toll-like Receptor FunctionOfer Levy; Fiscal Year: 2010..As a whole, these studies will deepen our understanding of how the unique physiology of the human newborn fundamentally alters innate immunity at birth. ..