title: Cutting edge: myeloid differentiation factor 88 deficiency improves resistance against sepsis caused by polymicrobial infection.
abstract: Toll-like receptors (TLRs) are important for the activation of innate immune cells upon encounter of microbial pathogens. The present study investigated the potential roles of TLR2, TLR4, and the signaling protein myeloid differentiation factor 88 (MyD88) in polymicrobial septic peritonitis. Whereas both TLR2 and TLR4 were dispensable for host defense against septic peritonitis, MyD88-deficient mice were protected in this infection model. Recruitment of neutrophils to the septic focus and bacterial clearance were normal in MyD88-deficient mice. In contrast, the systemic inflammatory response was strongly attenuated in the absence of MyD88. Surprisingly, MyD88 deficiency did not alter cytokine and chemokine production in spleen, but markedly reduced the inflammatory response in liver and lung. Production of monocyte chemoattractant protein-1 and macrophage-inflammatory protein-1alpha was entirely independent of MyD88. These results imply a central role of MyD88 for the systemic immune pathology of polymicrobial sepsis and show that cytokine production in spleen and induction of certain chemokines are MyD88 independent.
authors.affiliation: Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Weighardt
authors.forename: Simone
authors.initials: S
authors.lastname: Kaiser-Moore
authors.forename: Ramunas M
authors.initials: RM
authors.lastname: Vabulas
authors.forename: Carsten J
authors.initials: CJ
authors.lastname: Kirschning
authors.forename: Hermann
authors.initials: H
authors.lastname: Wagner
authors.forename: Bernhard
authors.initials: B
authors.lastname: Holzmann
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics* / Q000502:physiology; D001424:Bacterial Infections / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D018925:Chemokines / Q000096:biosynthesis / Q000097:blood; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D007113:Immunity, Innate / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D010538:Peritonitis / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D011971:Receptors, Immunologic / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D018805:Sepsis / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D018925:Chemokines; D016207:Cytokines; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic