Abstract

Project Goals and Objectives: Specific projects will 1) identify and characterize specific mechanisms used by pathogenic bacteria to evade or subvert normal phagocyte responses and therefore cause disease, and 2) investigate human phagocyte response mechanisms to pathogenic bacteria. Research Accomplishments: 1) We have determined that Group A Streptococcus secretes a homologue of human CD11b that blocks innate and acquired immune function. This represents a novel mechanism by which Group A Streptococcus can survive during the course of human infection. 2)We used human oligonucleotide microarrays (Affymetrix GeneChip) to determine global gene expression profiles in human PMNs during receptor-mediated phagocytosis. We discovered that gene transcription following phagocytosis serves mainly to determine PMN fate. We identified entire apoptotic pathways (>100 genes) for activated human PMNs and for those undergoing spontaneous apoptosis. These studies will be used as a springboard for studies with human pathogens.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000900-01
Application #
6546348
Study Section
(LHBP)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2001
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

DeLeo, Frank R; Diep, Binh An; Otto, Michael (2009) Host defense and pathogenesis in Staphylococcus aureus infections. Infect Dis Clin North Am 23:17-34
Kennedy, Adam D; DeLeo, Frank R (2009) Neutrophil apoptosis and the resolution of infection. Immunol Res 43:25-61
Koziel, Joanna; Maciag-Gudowska, Agnieszka; Mikolajczyk, Tomasz et al. (2009) Phagocytosis of Staphylococcus aureus by macrophages exerts cytoprotective effects manifested by the upregulation of antiapoptotic factors. PLoS One 4:e5210
Bubeck Wardenburg, Juliane; Palazzolo-Ballance, Amy M; Otto, Michael et al. (2008) Panton-Valentine leukocidin is not a virulence determinant in murine models of community-associated methicillin-resistant Staphylococcus aureus disease. J Infect Dis 198:1166-70
Palazzolo-Ballance, Amy M; Reniere, Michelle L; Braughton, Kevin R et al. (2008) Neutrophil microbicides induce a pathogen survival response in community-associated methicillin-resistant Staphylococcus aureus. J Immunol 180:500-9
Kennedy, Adam D; Willment, Janet A; Dorward, David W et al. (2007) Dectin-1 promotes fungicidal activity of human neutrophils. Eur J Immunol 37:467-78
Swindle, Emily J; Coleman, John W; DeLeo, Frank R et al. (2007) FcepsilonRI- and Fcgamma receptor-mediated production of reactive oxygen species by mast cells is lipoxygenase- and cyclooxygenase-dependent and NADPH oxidase-independent. J Immunol 179:7059-71
Quinn, Mark T; DeLeo, Frank R; Bokoch, Gary M (2007) Neutrophil methods and protocols. Preface. Methods Mol Biol 412:vii-viii
Burlak, Christopher; Hammer, Carl H; Robinson, Mary-Ann et al. (2007) Global analysis of community-associated methicillin-resistant Staphylococcus aureus exoproteins reveals molecules produced in vitro and during infection. Cell Microbiol 9:1172-90
Kobayashi, Scott D; Sturdevant, Dan E; DeLeo, Frank R (2007) Genome-scale transcript analyses in human neutrophils. Methods Mol Biol 412:441-53

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