In 2011, 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.

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Malachowa, Natalia; Freedman, Brett; Sturdevant, Daniel E et al. (2018) Differential Ability of Pandemic and Seasonal H1N1 Influenza A Viruses To Alter the Function of Human Neutrophils. mSphere 3:
Kobayashi, Scott D; Malachowa, Natalia; DeLeo, Frank R (2018) Neutrophils and Bacterial Immune Evasion. J Innate Immun :
Kobayashi, Scott D; Porter, Adeline R; Freedman, Brett et al. (2018) Antibody-Mediated Killing of Carbapenem-Resistant ST258 Klebsiella pneumoniae by Human Neutrophils. MBio 9:
Kobayashi, Scott D; Malachowa, Natalia; DeLeo, Frank R (2017) Influence of Microbes on Neutrophil Life and Death. Front Cell Infect Microbiol 7:159
Zhu, Luchang; Olsen, Randall J; Lee, Jessica D et al. (2017) Contribution of Secreted NADase and Streptolysin O to the Pathogenesis of Epidemic Serotype M1 Streptococcus pyogenes Infections. Am J Pathol 187:605-613
McGuinness, Will A; Kobayashi, Scott D; DeLeo, Frank R (2016) Evasion of Neutrophil Killing by Staphylococcus aureus. Pathogens 5:
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
Malachowa, Natalia; Kobayashi, Scott D; Quinn, Mark T et al. (2016) NET Confusion. Front Immunol 7:259
Zhu, Luchang; Olsen, Randall J; Nasser, Waleed et al. (2015) A molecular trigger for intercontinental epidemics of group A Streptococcus. J Clin Invest 125:3545-59
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

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