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Hematopoietic but not endothelial cell MyD88 contributes to host defense during gram-negative pneumonia derived sepsis.

ABSTRACT: Klebsiella pneumoniae is an important cause of sepsis. The common Toll-like receptor adapter myeloid differentiation primary response gene (MyD)88 is crucial for host defense against Klebsiella. Here we investigated the role of MyD88 in myeloid and endothelial cells during Klebsiella pneumosepsis. Mice deficient for MyD88 in myeloid (LysM-Myd88(-/-)) and myeloid plus endothelial (Tie2-Myd88(-/-)) cells showed enhanced lethality and bacterial growth. Tie2-Myd88(-/-) mice reconstituted with control bone marrow, representing mice with a selective MyD88 deficiency in endothelial cells, showed an unremarkable antibacterial defense. Myeloid or endothelial cell MyD88 deficiency did not impact on lung pathology or distant organ injury during late stage sepsis, while LysM-Myd88(-/-) mice demonstrated a strongly attenuated inflammatory response in the airways early after infection. These data suggest that myeloid but not endothelial MyD88 is important for host defense during gram-negative pneumonia derived sepsis.

SUBMITTER: van Lieshout MH

PROVIDER: S-EPMC4177915 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Hematopoietic but not endothelial cell MyD88 contributes to host defense during gram-negative pneumonia derived sepsis.

van Lieshout Miriam H P MH Anas Adam A AA Florquin Sandrine S Hou Baidong B van't Veer Cornelis C de Vos Alex F AF van der Poll Tom T

PLoS pathogens 20140925 9

Klebsiella pneumoniae is an important cause of sepsis. The common Toll-like receptor adapter myeloid differentiation primary response gene (MyD)88 is crucial for host defense against Klebsiella. Here we investigated the role of MyD88 in myeloid and endothelial cells during Klebsiella pneumosepsis. Mice deficient for MyD88 in myeloid (LysM-Myd88(-/-)) and myeloid plus endothelial (Tie2-Myd88(-/-)) cells showed enhanced lethality and bacterial growth. Tie2-Myd88(-/-) mice reconstituted with contro ...[more]

PMID: 25254554

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Hematopoietic but not endothelial cell MyD88 contributes to host defense during gram-negative pneumonia derived sepsis.

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Hematopoietic but not endothelial cell MyD88 contributes to host defense during gram-negative pneumonia derived sepsis.

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