title: MyD88, but not toll-like receptors 4 and 2, is required for efficient clearance of Brucella abortus.
abstract: It is not clear how the host initially recognizes and responds to infection by gram-negative pathogenic Brucella spp. It was previously shown (D. S. Weiss, B. Raupach, K. Takeda, S. Akira, and A. Zychlinsky, J. Immunol. 172:4463-4469, 2004) that the early macrophage response against gram-negative bacteria is mediated by Toll-like receptor 4 (TLR4), which signals in response to lipopolysaccharide (LPS). Brucella, however, has a noncanonical LPS which does not have potent immunostimulatory activity. We evaluated the kinetics of TLR4 activation and the cytokine response in murine macrophages after Brucella infection. We found that during infection of macrophages, Brucella avoids activation of TLR4 at 6 h but activates TLR4, TLR2, and myeloid differentiation factor 88 (MyD88) at 24 h postinfection. Interestingly, even though its activation is delayed, MyD88 is important for host defense against Brucella infection in vivo, since MyD88(-/-) mice do not clear the bacteria as efficiently as wild-type, TLR4(-/-), TLR2(-/-), or TLR4/TLR2(-/-) mice.
authors.affiliation: Max-Planck Institut für Infektionsbiologie, Campus Charite Mitte, Schumannstrasse 21/22, Berlin D-10117, Germany.
authors.forename: David S
authors.initials: DS
authors.lastname: Weiss
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Arturo
authors.initials: A
authors.lastname: Zychlinsky
authors.forename: Edgardo
authors.initials: E
authors.lastname: Moreno
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D002003:Brucella abortus / Q000276:immunology*; D002006:Brucellosis / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000382:microbiology; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D019779:Salmonella enterica / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D016207:Cytokines; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha