Abstract

Human polymorphonuclear leukocytes (PMNs or neutrophils) are essential to the innate immune response against invading microorganisms. In contrast to the acquired immune response, which requires time to develop and is dependent on previous interaction with specific pathogens, the ability of PMNs to kill infectious microorganisms is immediate, non-specific, and not dependent on previous pathogen exposure. Inasmuch as PMNs produce toxic microbicidal components and are the predominant immune cell in most bacterial infections, moderation of infection-induced inflammation is critical for limiting host tissue destruction. Recent evidence suggests PMN apoptosis facilitates resolution of bacterial infections, an idea supported by the finding that pathogens alter neutrophil apoptosis to survive. A key aspect of our research investigates how PMNs ingest and kill bacteria, and elucidates post-phagocytosis sequelae such as apoptosis, processes crucial for the resolution phase of inflammation. These studies established a global model of host cell-pathogen interaction that provides fundamental insight into the resolution of infection in humans.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000900-08
Application #
7732567
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2008
Total Cost
$806,192
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
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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