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Infection and Immunity, August 2005, p. 5137-5143, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.5137-5143.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

MyD88, but Not Toll-Like Receptors 4 and 2, Is Required for Efficient Clearance of Brucella abortus

David S. Weiss,1,2 Kiyoshi Takeda,3 Shizuo Akira,3 Arturo Zychlinsky,1* and Edgardo Moreno4

Max-Planck Institut fur Infektionsbiologie, Berlin D-10117, Germany,1 Department of Microbiology and Skirball Institute, NYU School of Medicine, New York, New York 10016,2 Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan,3 Programa de Investigacion en Enfermedades Tropicales, Escuela de Medicina Veterinaria, Universidad Nacional, Aptdo 304-3000 Heredia, Costa Rica4

Received 24 January 2005/ Returned for modification 2 March 2005/ Accepted 21 March 2005

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.

* Corresponding author. Mailing address: Max-Planck Institut für Infektionsbiologie, Campus Charite Mitte, Schumannstrasse 21/22, Berlin D-10117, Germany. Phone: 49 30 28 460 300. Fax: 49 30 28 460 301. E-mail: zychlinsky{at}mpiib-berlin.mpg.de.

Editor: J. N. Weiser

Infection and Immunity, August 2005, p. 5137-5143, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.5137-5143.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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