In FY2013, we investigated the role played by human polymorphonuclear leukocytes (PMNs or neutrophils) in host defense against bacterial pathogens. 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.

Project Start
Project End
Budget Start
Budget End
Support Year
13
Fiscal Year
2013
Total Cost
$211,548
Indirect Cost
City
State
Country
Zip Code
Kobayashi, Scott D; Sturdevant, Daniel E; Deleo, Frank R (2014) Genome-scale transcript analyses with human neutrophils. Methods Mol Biol 1124:437-50
Malech, Harry L; Deleo, Frank R; Quinn, Mark T (2014) The role of neutrophils in the immune system: an overview. Methods Mol Biol 1124:3-10
Lu, Thea; Porter, Adeline R; Kennedy, Adam D et al. (2014) Phagocytosis and killing of Staphylococcus aureus by human neutrophils. J Innate Immun 6:639-49
Siemsen, Daniel W; Malachowa, Natalia; Schepetkin, Igor A et al. (2014) Neutrophil isolation from nonhuman species. Methods Mol Biol 1124:19-37
Kobayashi, Scott D; Deleo, Frank R (2013) Systems biology and innate immunity. J Innate Immun 5:97-9
Voyich, Jovanka M; Vuong, Cuong; DeWald, Mark et al. (2009) The SaeR/S gene regulatory system is essential for innate immune evasion by Staphylococcus aureus. J Infect Dis 199:1698-706
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
Kennedy, Adam D; DeLeo, Frank R (2008) PI3K and NADPH oxidase: a class act. Blood 112:4788-9
Lu, Ling; Ma, Zhuo; Jokiranta, T Sakari et al. (2008) Species-specific interaction of Streptococcus pneumoniae with human complement factor H. J Immunol 181:7138-46