Journal
PLOS PATHOGENS
Volume 13, Issue 4, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.ppat.1006309
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Funding
- National Institute of Allergy and Infectious Diseases of the National Institutes of Health [R01AI118861, R00AI087963, T32GM007229, T32AI055400]
- National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health [R33EB019767]
- American Lung Association [RG-268528-N]
- American Heart Association [13BGIA14780070]
- Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Disease Award
- National Science Foundation CAREER Award [1350601]
- National Science Foundation [DGE-0822]
- NIH [1F32GM120929-01A1, RM1 HG007743]
- Center for Photogenomics
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [1350601] Funding Source: National Science Foundation
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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 Ly6C(hi) 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 Ly6C(hi) 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 IFN gamma responses, and monocytes are also required for TNF production. Moreover, natural killer (NK) cells, NKT cells, and gamma delta T cells are sources of IFN gamma, and monocytes direct IFN gamma production by these cell types. Thus, neutrophils and monocytes cooperate in eliciting an optimal cytokine response that promotes effective control of bacterial infection.
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