| First Author | Copin R | Year | 2007 |
| Journal | J Immunol | Volume | 178 |
| Issue | 8 | Pages | 5182-91 |
| PubMed ID | 17404301 | Mgi Jnum | J:145275 |
| Mgi Id | MGI:3834062 | Doi | 10.4049/jimmunol.178.8.5182 |
| Citation | Copin R, et al. (2007) MyD88-dependent activation of B220-CD11b+LY-6C+ dendritic cells during Brucella melitensis infection. J Immunol 178(8):5182-91 |
| abstractText | IFN-gamma is a key cytokine controlling Brucella infection. One of its major function is the stimulation of Brucella-killing effector mechanisms, such as inducible NO synthase (iNOS)/NOS2 activity, in phagocytic cells. In this study, an attempt to identify the main cellular components of the immune response induced by Brucella melitensis in vivo is made. IFN-gamma and iNOS protein were analyzed intracellularly using flow cytometry in chronically infected mice. Although TCRbeta(+)CD4(+) cells were the predominant source of IFN-gamma in the spleen, we also identified CD11b(+)LY-6C(+)LY-6G(-)MHC-II(+) cells as the main iNOS-producing cells in the spleen and the peritoneal cavity. These cells appear similar to inflammatory dendritic cells recently described in the mouse model of Listeria monocytogenes infection and human psoriasis: the TNF/iNOS-producing dendritic cells. Using genetically deficient mice, we demonstrated that the induction of iNOS and IFN-gamma-producing cells due to Brucella infection required TLR4 and TLR9 stimulation coupled to Myd88-dependent signaling pathways. The unique role of MyD88 was confirmed by the lack of impact of Toll-IL-1R domain-containing adaptor inducing IFN-beta deficiency. The reduction of IFN-gamma(+) and iNOS(+) cell frequency observed in MyD88-, TLR4-, and TLR9-deficient mice correlated with a proportional lack of Brucella growth control. Taken together, our results provide new insight into how immune responses fight Brucella infection. |
