Titel
Natural killer cell-intrinsic type I IFN signaling controls Klebsiella pneumoniae growth during lung infection
Autor*in
Masa Ivin
Max F. Perutz Laboratories, Universität Wien
Autor*in
Amy Dumigan
Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast
Autor*in
Filipe N. de Vasconcelos
Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast
... show all
Abstract
Klebsiella pneumoniae is a significant cause of nosocomial pneumonia and an alarming pathogen owing to the recent isolation of multidrug resistant strains. Understanding of immune responses orchestrating K. pneumoniae clearance by the host is of utmost importance. Here we show that type I interferon (IFN) signaling protects against lung infection with K. pneumoniae by launching bacterial growth-controlling interactions between alveolar macrophages and natural killer (NK) cells. Type I IFNs are important but disparate and incompletely understood regulators of defense against bacterial infections. Type I IFN receptor 1 (Ifnar1)-deficient mice infected with K. pneumoniae failed to activate NK cell-derived IFN-γ production. IFN-γ was required for bactericidal action and the production of the NK cell response-amplifying IL-12 and CXCL10 by alveolar macrophages. Bacterial clearance and NK cell IFN-γ were rescued in Ifnar1-deficient hosts by Ifnar1-proficient NK cells. Consistently, type I IFN signaling in myeloid cells including alveolar macrophages, monocytes and neutrophils was dispensable for host defense and IFN-γ activation. The failure of Ifnar1-deficient hosts to initiate a defense-promoting crosstalk between alveolar macrophages and NK cell was circumvented by administration of exogenous IFN-γ which restored endogenous IFN-γ production and restricted bacterial growth. These data identify NK cell-intrinsic type I IFN signaling as essential driver of K. pneumoniae clearance, and reveal specific targets for future therapeutic exploitations.
Stichwort
Klebsiella pneumoniaeNK cellsAlveolar macrophagesInterferonsInflammationMacrophagesImmune receptor signalingBacterial pathogens
Objekt-Typ
Sprache
Englisch [eng]
Persistent identifier
https://phaidra.univie.ac.at/o:912512
Erschienen in
Titel
PLOS Pathogens
Band
13
Ausgabe
11
Verlag
Public Library of Science (PLoS)
Erscheinungsdatum
2017
Zugänglichkeit
Rechteangabe
© 2017 Ivin et al

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