Interaction of the CD43 Sialomucin with the Mycobacterium tuberculosis Cpn60.2 Chaperonin Leads to Tumor Necrosis Factor Alpha Production

• Published in: Infection and immunity Vol. 85; no. 3
• Main Authors: Torres-Huerta, Alvaro, Villaseñor, Tomás, Flores-Alcantar, Angel, Parada, Cristina, Alemán-Navarro, Estefanía, Espitia, Clara, Pedraza-Alva, Gustavo, Rosenstein, Yvonne
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.03.2017
• Subjects: Bacterial Proteins - metabolism; Cell Line; Chaperonin 60 - metabolism; Host Response and Inflammation; Humans; Leukosialin - metabolism; Macrophages - immunology; Macrophages - metabolism; Macrophages - microbiology; Mycobacterium tuberculosis - physiology; NF-kappa B - metabolism; Protein Binding; Signal Transduction; Transcription Factor AP-1 - metabolism; Tumor Necrosis Factor-alpha - biosynthesis; Cpn60.2; macrophages; Mycobacterium tuberculosis; tumor necrosis factor alpha; cell signaling; CD43
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00915-16

is the causal agent of tuberculosis. Tumor necrosis factor alpha (TNF-α), transforming growth factor β (TGF-β), and gamma interferon (IFN-γ) secreted by activated macrophages and lymphocytes are considered essential to contain 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-α and that this production is CD43 dependent. In addition, we present evidence that the signaling pathway leading to TNF-α production upon interaction with Cpn60.2 requires active Src family kinases, phospholipase C-γ (PLC-γ), 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-α production and underscore an important role for CD43 in the host-mycobacterium interaction.