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Medientyp:
E-Artikel
Titel:
In vivo single‐cell transcriptomics reveal Klebsiella pneumoniae skews lung macrophages to promote infection
Beteiligte:
Dumigan, Amy;
Cappa, Oisin;
Morris, Brenda;
Sá Pessoa, Joana;
Calderon‐Gonzalez, Ricardo;
Mills, Grant;
Lancaster, Rebecca;
Simpson, David;
Kissenpfennig, Adrien;
Bengoechea, Jose A
Erschienen:
Springer Science and Business Media LLC, 2022
Erschienen in:EMBO Molecular Medicine
Sprache:
Englisch
DOI:
10.15252/emmm.202216888
ISSN:
1757-4676;
1757-4684
Entstehung:
Anmerkungen:
Beschreibung:
<jats:title>Abstract</jats:title><jats:p>The strategies deployed by antibiotic‐resistant bacteria to counteract host defences are poorly understood. Here, we elucidate a novel host–pathogen interaction resulting in skewing lung macrophage polarisation by the human pathogen <jats:italic>Klebsiella pneumoniae</jats:italic>. We identify interstitial macrophages (IMs) as the main population of lung macrophages associated with <jats:italic>Klebsiella</jats:italic>. Single‐cell transcriptomics and trajectory analysis of cells reveal type I IFN and IL10 signalling, and macrophage polarisation are characteristic of infected IMs, whereas Toll‐like receptor (TLR) and Nod‐like receptor signalling are features of infected alveolar macrophages. <jats:italic>Klebsiella</jats:italic>‐induced macrophage polarisation is a singular M2‐type we termed M(Kp). To rewire macrophages, <jats:italic>Klebsiella</jats:italic> hijacks a TLR‐type I IFN‐IL10‐STAT6 axis. Absence of STAT6 limits <jats:italic>Klebsiella</jats:italic> intracellular survival and facilitates the clearance of the pathogen <jats:italic>in vivo</jats:italic>. Glycolysis characterises M(Kp) metabolism, and inhibition of glycolysis results in clearance of intracellular <jats:italic>Klebsiella</jats:italic>. Capsule polysaccharide governs M(Kp). <jats:italic>Klebsiella</jats:italic> also skews human macrophage polarisation towards M(Kp) in a type I IFN‐IL10‐STAT6‐dependent manner. <jats:italic>Klebsiella</jats:italic> induction of M(Kp) represents a novel strategy to overcome host restriction, and identifies STAT6 as target to boost defences against <jats:italic>Klebsiella.</jats:italic></jats:p>