Interaction Of The Cd43 Sialomucin With The Mycobacterium Tuberculosis Cpn60.2 Chaperonin Leads To Tumor Necrosis Factor Alpha Production

Mycobacterium tuberculosis is the causal agent of tuberculosis. Tumor necrosis factor alpha (TNF- alpha), transforming growth factor beta (TGF-beta), and gamma interferon (IFN-gamma) secreted by activated macrophages and lymphocytes are considered essential to contain Mycobacterium tuberculosis infection. The CD43 sialomucin has been reported to act as a receptor for bacilli through its interaction with the chaperonin Cpn60.2, facilitating mycobacterium-macrophage contact. We report here that Cpn60.2 induces both human THP-1 cells and mouse-derived bone marrow- derived macrophages (BMMs) to produce TNF-alpha and that this production is CD43 dependent. In addition, we present evidence that the signaling pathway leading to TNF-alpha production upon interaction with Cpn60.2 requires active Src family kinases, phospholipase C-gamma (PLC-gamma), phosphatidylinositol 3-kinase (PI3K), p38, and Jun N-terminal protein kinase (JNK), both in BMMs and in THP-1 cells. Our data highlight the role of CD43 and Cpn60.2 in TNF-alpha production and underscore an important role for CD43 in the host-mycobacterium interaction.