title: 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.
authors.affiliation: Center of Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands; Center of Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Miriam H P
authors.initials: MH
authors.lastname: van Lieshout
authors.affiliation: Center of Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands; Center of Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Adam A
authors.initials: AA
authors.lastname: Anas
authors.affiliation: Department of Pathology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.affiliation: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chaoyang District, Beijing, China.
authors.forename: Baidong
authors.initials: B
authors.lastname: Hou
authors.affiliation: Center of Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands; Center of Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Cornelis
authors.initials: C
authors.lastname: van't Veer
authors.affiliation: Center of Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands; Center of Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Alex F
authors.initials: AF
authors.lastname: de Vos
authors.affiliation: 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.
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology*; D005260:Female; D054884:Host-Pathogen Interactions; D007113:Immunity, Innate / Q000276:immunology*; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D007710:Klebsiella Infections / Q000276:immunology* / Q000382:microbiology; D007711:Klebsiella pneumoniae; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology / Q000473:pathology*; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology*; D018410:Pneumonia, Bacterial / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000209:etiology*
chemical_list: D016207:Cytokines; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger