A role of interleukin-17A in modulating intracellular survival of Mycobacterium bovis BCG in murine macrophages

Abstract

Interleukin-17A has been demonstrated to participate in the pathogenesis of mycobacterial infections. Whether interleukin-17A regulates innate defense mechanisms of macrophage against mycobacteria remain to be elucidated. In the present study, we investigated the effects of interleukin-17A on modulating the intracellular survival of Mycobacterium bovis BCG in RAW264.7 macrophages. Our data revealed that the clearance of intracellular BCG in macrophages was significantly enhanced by interleukin-17A pretreatment. Moreover, interleukin-17A-enhanced clearance of intracellular BCG could be abrogated by addition of inducible nitric oxide synthase inhibitor. We observed that interleukin-17A pretreatment was able to synergistically enhance both nitric oxide production and inducible nitric oxide synthase expression in BCG-infected macrophages in dose- and time-dependent manner. We also revealed that interleukin-17A was able to specifically enhance BCG-induced phosphorylation of JNK, but not ERK1/2 or p38 MAPK. By using specific JNK inhibitor SP600125, the production of nitric oxide in BCG-infected macrophages with interleukin-17A pretreatment was significantly suppressed. Taken together, we confirmed the involvement of JNK pathway in interleukin-17A-enhanced nitric oxide production in BCG-infected macrophages. In conclusion, our study revealed an anti-mycobacterial role of interleukin-17A through priming the macrophages to produce nitric oxide in response to mycobacteria infection.