Interleukin 6 Promotes<i>Brucella abortus</i>Clearance by Controlling Bactericidal Activity of Macrophages and CD8⁺T Cell Differentiation

Abstract

To date, the implications of interleukin 6 (IL-6) for immune responses in the context of <i>Brucella</i> infection are still unknown. In the present study, we found that <i>Brucella abortus</i> infection induced marked production of IL-6 in mice that was important for sufficient differentiation of CD8⁺ T cells, a key factor in <i>Brucella</i> clearance. Blocking IL-6 signaling also significantly induced serum IL-4 and IL-10, together with a decreased gamma interferon (IFN-γ) level, suggesting that IL-6 is essential for priming the T-helper (Th) 1 cell immune response during <i>Brucella</i> infection. The IL-6 pathway also activated the bactericidal activity of primary and cultured macrophages. Bacterial killing was markedly abrogated when IL-6 signaling was suppressed, and this phenomenon was mainly associated with decreased activity of lysosome-mediated killing. Interestingly, suppressor of cytokine signaling 3 (SOCS3) was important for regulating the IL-6-dependent anti-<i>Brucella</i> activity through the JAK/STAT pathway. During early infection, in the absence of SOCS3, IL-6 exhibited anti-inflammatory effects and lysosome-mediated killing inhibition; however, the increase in SOCS3 successfully shifted functional IL-6 toward proinflammatory brucellacidal activity in the late stage. Our data clearly indicate that IL-6 contributes to host resistance against <i>B. abortus</i> infection by controlling brucellacidal activity in macrophages and priming cellular immune responses.