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

Miriam H P van Lieshout*, Adam A Anas, Sandrine Florquin, Baidong Hou, Cornelis van't Veer, Alex F de Vos, Tom van der Poll

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

24 Citations (Scopus)
8 Downloads (Pure)

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.

Original languageEnglish
Article numbere1004368
JournalPLoS Pathogens
Volume10
Issue number9
DOIs
Publication statusPublished - 25 Sept 2014
Externally publishedYes

Bibliographical note

Funding:
MHPvL and AAA were supported by a grant from the Academic Medical Centre Graduate School of Medical Sciences (http://www.amc.nl/web/
Onderwijs/PhD/Graduate-School.htm). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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