MyD88, but not toll-like receptors 4 and 2, is required for efficient clearance of Brucella abortus.
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.
Weiss
David S
DS
Max-Planck Institut für Infektionsbiologie, Campus Charite Mitte, Schumannstrasse 21/22, Berlin D-10117, Germany.
Takeda
Kiyoshi
K
Akira
Shizuo
S
Zychlinsky
Arturo
A
Moreno
Edgardo
E
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
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