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Hematopoietic but not endothelial cell MyD88 contributes to host defense during gram-negative pneumonia derived sepsis.
PLoS Pathog 2014; 10(9):e1004368PP

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.

Authors+Show Affiliations

Center of Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands; Center of Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands.Center of Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands; Center of Experimental and Molecular Medicine, 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.Center of Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands; Center of Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands.Center of Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands; Center of Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands.Center of Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands; Center of Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands; Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25254554

Citation

van Lieshout, Miriam H P., et al. "Hematopoietic but Not Endothelial Cell MyD88 Contributes to Host Defense During Gram-negative Pneumonia Derived Sepsis." PLoS Pathogens, vol. 10, no. 9, 2014, pp. e1004368.
van Lieshout MH, Anas AA, Florquin S, et al. Hematopoietic but not endothelial cell MyD88 contributes to host defense during gram-negative pneumonia derived sepsis. PLoS Pathog. 2014;10(9):e1004368.
van Lieshout, M. H., Anas, A. A., Florquin, S., Hou, B., van't Veer, C., de Vos, A. F., & van der Poll, T. (2014). Hematopoietic but not endothelial cell MyD88 contributes to host defense during gram-negative pneumonia derived sepsis. PLoS Pathogens, 10(9), pp. e1004368. doi:10.1371/journal.ppat.1004368.
van Lieshout MH, et al. Hematopoietic but Not Endothelial Cell MyD88 Contributes to Host Defense During Gram-negative Pneumonia Derived Sepsis. PLoS Pathog. 2014;10(9):e1004368. PubMed PMID: 25254554.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hematopoietic but not endothelial cell MyD88 contributes to host defense during gram-negative pneumonia derived sepsis. AU - van Lieshout,Miriam H P, AU - Anas,Adam A, AU - Florquin,Sandrine, AU - Hou,Baidong, AU - van't Veer,Cornelis, AU - de Vos,Alex F, AU - van der Poll,Tom, Y1 - 2014/09/25/ PY - 2014/02/01/received PY - 2014/07/31/accepted PY - 2014/9/26/entrez PY - 2014/9/26/pubmed PY - 2015/12/15/medline SP - e1004368 EP - e1004368 JF - PLoS pathogens JO - PLoS Pathog. VL - 10 IS - 9 N2 - 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. SN - 1553-7374 UR - https://www.unboundmedicine.com/medline/citation/25254554/Hematopoietic_but_not_endothelial_cell_MyD88_contributes_to_host_defense_during_gram_negative_pneumonia_derived_sepsis_ L2 - http://dx.plos.org/10.1371/journal.ppat.1004368 DB - PRIME DP - Unbound Medicine ER -