title: Neutrophils and Ly6Chi monocytes collaborate in generating an optimal cytokine response that protects against pulmonary Legionella pneumophila infection.
abstract: Early responses mounted by both tissue-resident and recruited innate immune cells are essential for host defense against bacterial pathogens. In particular, both neutrophils and Ly6Chi monocytes are rapidly recruited to sites of infection. While neutrophils and monocytes produce bactericidal molecules, such as reactive nitrogen and oxygen species, both cell types are also capable of synthesizing overlapping sets of cytokines important for host defense. Whether neutrophils and monocytes perform redundant or non-redundant functions in the generation of anti-microbial cytokine responses remains elusive. Here, we sought to define the contributions of neutrophils and Ly6Chi monocytes to cytokine production and host defense during pulmonary infection with Legionella pneumophila, responsible for the severe pneumonia Legionnaires' disease. We found that both neutrophils and monocytes are critical for host defense against L. pneumophila. Both monocytes and neutrophils contribute to maximal IL-12 and IFNγ responses, and monocytes are also required for TNF production. Moreover, natural killer (NK) cells, NKT cells, and γδ T cells are sources of IFNγ, and monocytes direct IFNγ production by these cell types. Thus, neutrophils and monocytes cooperate in eliciting an optimal cytokine response that promotes effective control of bacterial infection.
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Cierra N
authors.initials: CN
authors.lastname: Casson
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Doerner
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Copenhaver
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Jasmine
authors.identifier: http://orcid.org/0000-0003-3882-0760
authors.initials: J
authors.lastname: Ramirez
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Alicia M
authors.identifier: http://orcid.org/0000-0002-4987-5030
authors.initials: AM
authors.lastname: Holmgren
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Boyer
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Ingharan J
authors.initials: IJ
authors.lastname: Siddarthan
authors.affiliation: Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Sara H
authors.initials: SH
authors.lastname: Rouhanifard
authors.affiliation: Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Arjun
authors.identifier: http://orcid.org/0000-0002-2915-6960
authors.initials: A
authors.lastname: Raj
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Sunny
authors.identifier: http://orcid.org/0000-0001-5214-9577
authors.initials: S
authors.lastname: Shin
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016952:Legionella pneumophila / Q000502:physiology*; D007877:Legionnaires' Disease / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D008168:Lung / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*
chemical_list: D000950:Antigens, Ly; D016207:Cytokines; C494192:Ly-6C antigen, mouse