Modulation of mycobacterium bovis (BCG)-induced cytokine response by IL-17

Abstract

Bacillus Calmette-Guerin (BCG) has been used to study the host immunity against mycobacteria infection. Proinflammatory cytokines including IL-6 are produced as part of host defense mechanisms to inhibit mycobacterial growth. Concerted regulation of inflammation is critical in controlling mycobacterial infection. IL-17A is a proinflammatory cytokine produced by T-helper 17 cells. It regulates innate immunity by activating the induction of other proinflammatory cytokines such as TNF-α from macrophages. We postulate IL-17A plays a critical role in regulating inflammatory responses against mycobacteria. Here, we examined whether IL-17A modulate BCG-induced cytokines production in primary human blood macrophages (PBMac). PBMac were pretreated with IL- 17A for 24h before BCG infection. Cytokine mRNA and protein levels were measured by quantitative RT-PCR and ELISA, respectively. The results demonstrated that IL-17A alone did not induce IL-6 production from PBMac but it enhanced BCG-induced IL-6 production dose-dependently at both RNA and protein levels. However, IL-17A did not have significant effect on the levels of TNF-α induced by BCG. We are currently delineating the signaling mechanisms of the enhancing effect of IL-17A on the cytokines production by macrophages. In conclusion, IL-17A could enhance the BCG-induced proinflammatory cytokine responses and play a role in coordinating immune response against mycobacterial infection.