title: Signaling lymphocyte-activation molecule SLAMF1 augments mycobacteria BCG-induced inflammatory response and facilitates bacterial clearance.
abstract: Tuberculosis, which is caused by intracellular mycobacterium Mycobacterium tuberculosis (Mtb), remains one of the most serious global public health concerns. The mechanisms by which innate immunity regulates the inflammatory responses and affects mycobacterial infection remain unclear. In this study, signaling lymphocyte-activation molecule family 1 (SLAMF1) was significantly upregulated in Mycobacterium bovis Bacille Calmette-Guérin (BCG)-infected RAW264.7 cells. Overexpression of SLAMF1 significantly increased the production of inflammatory factors TNF-α and IL-1β, as well as chemokine MCP-1, both in vitro and in vivo upon mycobacteria BCG infection. By contrast, knockdown of SLAMF1 significantly decreased the production of TNF-α, IL-1β, and MCP-1. Western blot analysis indicated that the NF-κB signaling pathway may contribute to the elevated inflammatory response promoted by SLAMF1, as evidenced by higher levels of phosphorylated p65 and IκBα detected with SLAMF1 overexpression. Furthermore, SLAMF1 upregulation facilitated bacterial clearance in infected RAW264.7 cells and in the lungs of infected mice. In conclusion, we demonstrated that BCG infection significantly upregulated SLAMF1, which enhanced inflammatory response by activating the NF-κB signaling pathway and facilitated bacterial clearance in BCG-infected RAW264.7 cells and mice.
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, PR China.
authors.forename: Tengfei
authors.initials: T
authors.lastname: Song
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, PR China.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Dong
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, PR China. Electronic address: sdxiongfd@126.com.
authors.forename: Sidong
authors.initials: S
authors.lastname: Xiong
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D009163:Mycobacterium bovis / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D011956:Receptors, Cell Surface; C000604062:Slamf1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
keywords: Inflammation; Macrophage; Mycobacteria; SLAMF1; Tuberculosis