%0 Journal Article
%1 10.1371/journal.ppat.1006696
%A Ivin, M
%A Dumigan, A
%A de Vasconcelos, F N
%A Ebner, F
%A Borroni, M
%A Kavirayani, A
%A Przybyszewska, K N
%A Ingram, R J
%A Lienenklaus, S
%A Kalinke, U
%A Stoiber, D
%A Bengoechea, J A
%A Kovarik, P
%D 2017
%E Pathog, PLoS
%I Public Library of Science
%J PLOS Pathog
%K kalinke
%N 11
%P 1-29
%T Natural killer cell-intrinsic type I IFN signaling controls Klebsiella pneumoniae growth during lung infection
%U https://doi.org/10.1371/journal.ppat.1006696
%V 13
%X Author summary The isolation of multidrug-resistant Klebsiella pneumoniae strains has significantly narrowed, or in some settings completely removed, the therapeutic options for the treatment of Klebsiella infections. Therapies targeting the immune system rather than the pathogen represent important alternatives. Despite the clinical relevance, there are still major gaps in our understanding of immune responses which drive the clearance of this pathogen. Type I interferons (IFNs) are known as powerful immune system regulators yet their effects on bacterial infections are disparate and remain elusive. In this study we show that type I IFN signaling is indispensable for mounting a protective and bacterial clearance-promoting immune response against K. pneumoniae. K. pneumoniae-induced type I IFNs launch a crosstalk between alveolar macrophages and NK cells by enabling NK cell IFN-γ production which in turn activates the macrophage anti-microbial armament. Type I IFN-responsive NK cells or IFN-γ administration rescue K. pneumoniae clearance in type I IFN-unresponsive hosts. Our study suggests that manipulation of type I IFN or IFN-γ levels might represent a valid strategy for treatment of drug-resistant K. pneumoniae infections.