title: IL-37 Expression is Upregulated in Patients with Tuberculosis and Induces Macrophages Towards an M2-like Phenotype.
abstract: Interleukin-37 (IL-37), a member of the IL-1 family, primarily functions as an anti-inflammatory cytokine, reducing inflammation and suppressing the immune response. However, the expression and role of IL-37 in tuberculosis (TB) remains unknown. We aimed to measure serum levels of IL-37 and several important cytokines in 25 patients with active TB and to analyse their association with disease activity. We found that IL-37 levels decreased in patients with TB and recovered after treatment. IL-37 levels negatively correlated with the serum concentration of IFN-γ and IL-12 but positively correlated with IL-10 and TGF-β levels. After IL-37, secretion was blocked in peripheral blood mononuclear cells from active patients with TB, IFN-γ and IL-10 production was significantly upregulated; this was not observed in healthy donors or patients after treatment. IL-37 knockdown significantly enhanced the phagocytic activity of THP1-derived macrophages towards Mycobacterium tuberculosis (M. tb). M1/M2 polarization-associated markers were detected simultaneously, and IL-37 induced a phenotypic shift in THP1-derived macrophages towards a high CD206(+) and low CD86(+) macrophage subtype. Furthermore, this phenotypic shift was accompanied by upregulated mRNA levels of arginase 1, TGF-β and IL-10, which are characteristic hallmarks of M2 macrophages. In conclusion, our results suggest that increased levels of IL-37 in patients with TB are associated with IFN-γ, IL-12, IL-10 and TGF-β levels and that IL-37 plays a pathological role in TB infection by inhibiting the production of pro-inflammatory cytokines and inducing macrophages towards an M2-like phenotype. Thus, IL-37 may be a novel research target to understand the pathogenesis of TB infection.
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.|Department of Laboratory Medicine, Longgang Central District Hospital, Shenzhen, Guangdong, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Laboratory Medicine, People's Hospital of Linyi, Linyi, Shandong, China.
authors.forename: C
authors.initials: C
authors.lastname: Gao
authors.affiliation: School of Nursing, Guangdong Medical College, Dongguan, Guangdong, China.
authors.forename: X
authors.initials: X
authors.lastname: Chi
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Y W
authors.initials: YW
authors.lastname: Hu
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: L
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: T
authors.initials: T
authors.lastname: Zeng
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use; D001119:Arginase / Q000235:genetics; D051940:B7-2 Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D004977:Ethambutol / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics; D053765:Interleukin-12 Subunit p35 / Q000097:blood; D007538:Isoniazid / Q000627:therapeutic use; D037181:Lectins, C-Type / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000276:immunology*; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D010641:Phenotype; D011718:Pyrazinamide / Q000627:therapeutic use; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface / Q000378:metabolism; D012293:Rifampin / Q000627:therapeutic use; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000097:blood / Q000235:genetics; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000995:Antitubercular Agents; D051940:B7-2 Antigen; C497964:CD86 protein, human; C508609:IL10 protein, human; C508858:IL12A protein, human; C508587:IL37 protein, human; D007375:Interleukin-1; D053765:Interleukin-12 Subunit p35; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D011718:Pyrazinamide; D009569:Nitric Oxide; D007371:Interferon-gamma; D004977:Ethambutol; C574619:ARG1 protein, human; D001119:Arginase; D007538:Isoniazid; D012293:Rifampin