TLR-2 mediated cytosolic-Ca²⁺ surge activates ER-stress-superoxide-NO signalosome augmenting TNF-α production leading to apoptosis of Mycobacterium smegmatis-infected fish macrophages.

ABSTRACT: The implications of TLR-2 mediated alterations in cytosolic-Ca²⁺((Ca²⁺)_c) levels in M. smegmatis infections is not well known. Using headkidney macrophages (HKM) from Clarias gariepinus, we observed TLR-2 signalling is required in the phagocytosis of M. smegmatis. M. smegmatis induced caspase-dependent HKM apoptosis in MOI, time and growth-phase dependent manner. RNAi and inhibitor studies demonstrated critical role of TLR-2 in eliciting (Ca²⁺)_c-surge and c-Src-PI3K-PLC axis playing an intermediary role in the process. The (Ca²⁺)_c-surge triggered downstream ER-stress and superoxide (O₂^-) generation. The cross-talk between ER-stress and O₂^- amplified TNF-α production, whi

SUBMITTER: Hussain MA 

PROVIDER: S-EPMC6707155 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature