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* Department of Biochemistry and Immunology and
Department of Microbiology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte-Minas Gerais, Brazil
Brucella abortus is a facultative intracellular bacterium that infects humans and domestic animals. The enhanced susceptibility to virulent B. abortus observed in MyD88 knockout (KO) mice led us to investigate the mechanisms involved in MyD88-dependent immune responses. First, we defined the role of MyD88 in dendritic cell (DC) maturation. In vitro as well as in vivo, B. abortus-exposed MyD88 KO DCs displayed a significant impairment on maturation as observed by expression of CD40, CD86, and MHC class II on CD11c+ cells. In addition, IL-12 and TNF-
production was totally abrogated in MyD88 KO DCs and macrophages. Furthermore, B. abortus-induced IL-12 production was found to be dependent on TLR2 in DC, but independent on TLR2 and TLR4 in macrophages. Additionally, we investigated the role of exogenous IL-12 and TNF- administration on MyD88 KO control of B. abortus infection. Importantly, IL-12, but not TNF-, was able to partially rescue host susceptibility in MyD88 KO-infected animals. Furthermore, we demonstrated the role played by TLR9 during virulent B. abortus infection. TLR9 KO-infected mice showed 1 log Brucella CFU higher than wild-type mice. Macrophages and DC from TLR9 KO mice showed reduced IL-12 and unaltered TNF- production when these cells were stimulated with Brucella. Together, these results suggest that susceptibility of MyD88 KO mice to B. abortus is due to impaired DC maturation and lack of IL-12 synthesis. Additionally, DC activation during Brucella infection plays an important regulatory role by stimulating and programming T cells to produce IFN-
.
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1 This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), CNPq/Centro Brasil Argentino de Biotecnologia, Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), and FAPEMIG/Pronex.
2 G.C.M. and D.M.M. equally contributed to this study.
3 Address correspondence and reprint requests to Dr. Sergio Costa Oliveira, Laboratory of Immunology of Infectious Diseases, Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte-Minas Gerais, Brazil, 31270-901. E-mail address: scozeus{at}icb.ufmg.br
4 Abbreviations used in this paper: DC, dendritic cell; HKBA, heat-killed Brucella abortus; KO, knockout; MHCII, MHC class II; BM, bone marrow.
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  W. Sukhumavasi, C. E. Egan, A. L. Warren, G. A. Taylor, B. A. Fox, D. J. Bzik, and E. Y. Denkers TLR Adaptor MyD88 Is Essential for Pathogen Control during Oral Toxoplasma gondii Infection but Not Adaptive Immunity Induced by a Vaccine Strain of the Parasite J. Immunol., September 1, 2008; 181(5): 3464 - 3473. [Abstract] [Full Text] [PDF]
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