Hematopoietic but Not Endothelial Cell MyD88 Contributes to Host Defense during Gram-negative Pneumonia Derived Sepsis

PLoS Pathogens

Adam A. Anas¹  Baidong Hou¹  Miriam H. P. van Lieshout²  Tom van der Poll²  Sandrine Florquin²  Cornelis van't Veer³  Alex F. de Vos⁴ 

[1] Center of Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands;Center of Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands;Department of Pathology, Academic Medical Center, Amsterdam, the Netherlands;Key Laboratory of Infection and Immunity, Institute of Biophysics, Chaoyang District, Beijing, China

关键词: Klebsiella infections;    Klebsiella pneumoniae;    Endothelial cells;    Bone marrow transplantation;    Neutrophils;    Sepsis;    Inflammation;    Pneumonia;   

DOI  :  10.1371/journal.ppat.1004368

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY