Natural killer cell-intrinsic type I IFN signaling controls Klebsiella pneumoniae growth during lung infection.

2.50
Hdl Handle:
http://hdl.handle.net/10033/621189
Title:
Natural killer cell-intrinsic type I IFN signaling controls Klebsiella pneumoniae growth during lung infection.
Authors:
Ivin, Masa; Dumigan, Amy; de Vasconcelos, Filipe N; Ebner, Florian; Borroni, Martina; Kavirayani, Anoop; Przybyszewska, Kornelia N; Ingram, Rebecca J; Lienenklaus, Stefan; Kalinke, Ulrich ( 0000-0003-0503-9564 ) ; Stoiber, Dagmar; Bengoechea, Jose A; Kovarik, Pavel
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.
Affiliation:
TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH, Feodor-Lynen-Str.7 30625 Hannover, Germany.
Citation:
Natural killer cell-intrinsic type I IFN signaling controls Klebsiella pneumoniae growth during lung infection. 2017, 13 (11):e1006696 PLoS Pathog.
Journal:
PLoS pathogens
Issue Date:
Nov-2017
URI:
http://hdl.handle.net/10033/621189
DOI:
10.1371/journal.ppat.1006696
PubMed ID:
29112952
Type:
Article
Language:
en
ISSN:
1553-7374
Appears in Collections:
publications of the department of experimental infection research ([TC] EXPI)

Full metadata record

DC FieldValue Language
dc.contributor.authorIvin, Masaen
dc.contributor.authorDumigan, Amyen
dc.contributor.authorde Vasconcelos, Filipe Nen
dc.contributor.authorEbner, Florianen
dc.contributor.authorBorroni, Martinaen
dc.contributor.authorKavirayani, Anoopen
dc.contributor.authorPrzybyszewska, Kornelia Nen
dc.contributor.authorIngram, Rebecca Jen
dc.contributor.authorLienenklaus, Stefanen
dc.contributor.authorKalinke, Ulrichen
dc.contributor.authorStoiber, Dagmaren
dc.contributor.authorBengoechea, Jose Aen
dc.contributor.authorKovarik, Pavelen
dc.date.accessioned2017-11-29T15:45:30Z-
dc.date.available2017-11-29T15:45:30Z-
dc.date.issued2017-11-
dc.identifier.citationNatural killer cell-intrinsic type I IFN signaling controls Klebsiella pneumoniae growth during lung infection. 2017, 13 (11):e1006696 PLoS Pathog.en
dc.identifier.issn1553-7374-
dc.identifier.pmid29112952-
dc.identifier.doi10.1371/journal.ppat.1006696-
dc.identifier.urihttp://hdl.handle.net/10033/621189-
dc.description.abstractKlebsiella 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.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAnimalsen
dc.subject.meshDrug Resistance, Multipleen
dc.subject.meshInterferon Type Ien
dc.subject.meshKiller Cells, Naturalen
dc.subject.meshKlebsiella Infectionsen
dc.subject.meshKlebsiella pneumoniaeen
dc.subject.meshMacrophages, Alveolaren
dc.subject.meshMiceen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshMice, Knockouten
dc.subject.meshReceptor Cross-Talken
dc.subject.meshRespiratory Tract Infectionsen
dc.subject.meshSignal Transductionen
dc.titleNatural killer cell-intrinsic type I IFN signaling controls Klebsiella pneumoniae growth during lung infection.en
dc.typeArticleen
dc.contributor.departmentTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH, Feodor-Lynen-Str.7 30625 Hannover, Germany.en
dc.identifier.journalPLoS pathogensen

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