Inactivation of the Type IV secretion system reduces the Th1 polarization of the immune response to Brucella abortus infection

University of California at Davis, Department of Medical Microbiology & Immunology, One Shields Avenue, Davis, CA 95616; Texas A&M University System Health Science Center, Department of Medical Microbiology & Immunology, College Station, TX 77843-1114

^* To whom correspondence should be addressed. Email: rmtsolis{at}ucdavis.edu.

	Abstract

The Brucella abortus Type IV secretion system (T4SS), encoded by the virB operon, is essential for establishing persistent infection in the murine reticuloendothelial system. To gain insight into the in vivo interactions mediated by the T4SS, we compared host responses elicited by B. abortus and with an isogenic mutant in the virB operon. Mice infected with the B. abortus virB mutant elicited smaller increases in serum levels of IgG2a, IFN- and IL-12p40 when compared with mice infected with B. abortus wild type. Despite equal bacterial loads in the spleen, at 3-4d post infection, levels of IFN- were higher in mice infected with wild type B. abortus than in mice infected with the virB mutant, as shown by real-time PCR, intracellular cytokine staining and cytokine levels. IFN- producing CD4⁺ T cells were more abundant in spleens of mice infected with wild type B. abortus, than in virB mutant-infected mice. Similar numbers of IFN- -secreting CD8⁺ T cells were observed in the spleens of infected mice with B. abortus 2308 or a virB mutant. These results suggest that early differences in cytokine responses contribute to a stronger Th1 polarization of the immune response in mice infected with wild type B. abortus, than in mice infected with the virB mutant.