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
Malachowa, Natalia; Kobayashi, Scott D; Quinn, Mark T et al. (2016) NET Confusion. Front Immunol 7:259
Kobayashi, Scott D; Porter, Adeline R; Dorward, David W et al. (2016) Phagocytosis and Killing of Carbapenem-Resistant ST258 Klebsiella pneumoniae by Human Neutrophils. J Infect Dis 213:1615-22
McGuinness, Will A; Kobayashi, Scott D; DeLeo, Frank R (2016) Evasion of Neutrophil Killing by Staphylococcus aureus. Pathogens 5:
Zhu, Luchang; Olsen, Randall J; Nasser, Waleed et al. (2015) A molecular trigger for intercontinental epidemics of group A Streptococcus. J Clin Invest :
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
Siemsen, Daniel W; Malachowa, Natalia; Schepetkin, Igor A et al. (2014) Neutrophil isolation from nonhuman species. Methods Mol Biol 1124:19-37
Schwartz, Justin T; Bandyopadhyay, Sarmistha; Kobayashi, Scott D et al. (2013) Francisella tularensis alters human neutrophil gene expression: insights into the molecular basis of delayed neutrophil apoptosis. J Innate Immun 5:124-36
Kobayashi, Scott D; Deleo, Frank R (2013) Systems biology and innate immunity. J Innate Immun 5:97-9
Lu, Thea; Kobayashi, Scott D; Quinn, Mark T et al. (2012) A NET Outcome. Front Immunol 3:365

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