Bacterial Manipulation of NK Cell Regulatory Activity Increases Susceptibility to Listeria monocytogenes Infection.
Natural killer (NK) cells produce interferon (IFN)-γ and thus have been suggested to promote type I immunity during bacterial infections. Yet, Listeria monocytogenes (Lm) and some other pathogens encode proteins that cause increased NK cell activation. Here, we show that stimulation of NK cell activation increases susceptibility during Lm infection despite and independent from robust NK cell production of IFNγ. The increased susceptibility correlated with IL-10 production by responding NK cells. NK cells produced IL-10 as their IFNγ production waned and the Lm virulence protein p60 promoted induction of IL-10 production by mouse and human NK cells. NK cells consequently exerted regulatory effects to suppress accumulation and activation of inflammatory myeloid cells. Our results reveal new dimensions of the role played by NK cells during Lm infection and demonstrate the ability of this bacterial pathogen to exploit the induction of regulatory NK cell activity to increase host susceptibility.
Department of Biomedical Sciences, National Jewish Health, Denver, Colorado, United States of America.|Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
Sarah E
0000-0002-5975-5032
SE
Clark
Department of Biomedical Sciences, National Jewish Health, Denver, Colorado, United States of America.
Holly C
HC
Filak
Department of Biomedical Sciences, National Jewish Health, Denver, Colorado, United States of America.|Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
Brandon S
BS
Guthrie
Department of Biomedical Sciences, National Jewish Health, Denver, Colorado, United States of America.
Rebecca L
RL
Schmidt
Department of Molecular and Cell Biology, Division of Immunology, University of California, Berkeley, Berkeley, California, United States of America.
Amanda
A
Jamieson
Division of Pathology, Department of Medicine, National Jewish Health, Denver, Colorado, United States of America.
Patricia
P
Merkel
Division of Pathology, Department of Medicine, National Jewish Health, Denver, Colorado, United States of America.
Vijaya
V
Knight
Department of Pediatrics, National Jewish Health, Denver, Colorado, United States of America.
Caroline M
CM
Cole
Department of Molecular and Cell Biology, Division of Immunology, University of California, Berkeley, Berkeley, California, United States of America.
David H
DH
Raulet
Department of Biomedical Sciences, National Jewish Health, Denver, Colorado, United States of America.|Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
Laurel L
LL
Lenz
D019264:Adoptive Transfer; D000818:Animals; D018920:Coculture Techniques; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
C556062:IL10 protein, mouse; D016753:Interleukin-10