No abstract

Chronic bacterial diseases such as Brucellosis may result from the pathogen’s ability to evade the initial immune response. Moreover, since Brucella spp. is known to target phagocytes, we investigated its effects on macrophage (mø) phenotype and induction of anti-inflammatory responses. Brucella did not induce alternative activation of mø in cultured bone marrow-derived mø (BMM) or in splenic CD11b+ cells isolated from mice during early infection. However, upregulation of interleukin 10 (IL-10) in serum, spleen and splenic mø from B. abortus infected mice was observed as early as 3 days post infection. Infection of BMM from MyD88-/-, TLR2-/-, TLR4-/-, TLR2/4-/- and TLR9-/- mice demonstrated that IL-10 induction was MyD88 dependent and was partially dependent on pathogen recognition by TLR2 and TLR4. Functionally, in vitro IL-10-/- BMM infection resulted in significantly higher pro-inflammatory cytokine production and decreased bacterial intracellular survival. In vivo 9 days infection of IL-10-/- mice confirmed a lower ability of B. abortus to survive in absence of IL-10, as well as higher induction of pro-inflammatory cytokines, resulting in increased pathology in liver and spleen of infected mice. Taken together, our results suggest that early IL-10 induction by infected mø contributes to an initial balance between pro-inflammatory and anti-inflammatory cytokines that is beneficial to the pathogen, thereby leading to enhanced bacterial survival and persistent infection.