title: Interleukin 24 as a novel potential cytokine immunotherapy for the treatment of Mycobacterium tuberculosis infection.
abstract: Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) remains a major global health problem. Interleukin 24 (IL-24) is a novel tumor suppressor and a unique member of the IL-10 family of cytokines. However, the in vivo immunological consequences of this cytokine's activity during Mtb infection are still unknown. We found that IL-24 concentration was significantly decreased in the sera of TB patients, and Mtb infection suppressed IL-24 expression of human peripheral blood mononuclear cells (PBMCs) in vitro. Furthermore, we used a mouse infection model utilizing the virulent Mtb H37Rv strain to demonstrate that the administration of exogenous IL-24 had a protective effect against the bacteria. We found that IL-24 could activate human CD8(+) T cells, driving CD8(+) T cells to produce interferon-γ (IFN-γ) and counteract TB. This activity was found to be dependent on early involvement of neutrophils in the mouse model. IL-24 strongly stimulated IFN-γ production mainly by signaling through the IL-24 receptors of human CD8(+) T cells. IL-12 secretion from neutrophils in response to IL-24 treatment might be a minor factor in activating human CD8(+) T cells to secrete IFN-γ. Suppression of IL-24 expression by Mtb infection might enhance susceptibility to infection and promote the development of chronic TB. This new information could potentially stimulate the development of a new cytokine-based immunotherapeutic approach using IL-24 to stimulate immunity against TB.
authors.affiliation: State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immune-related Diseases, Wuhan University School of Medicine, Wuhan 430071, PR China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Ma
authors.forename: Hai-Dan
authors.initials: HD
authors.lastname: Chen
authors.forename: Yubin
authors.initials: Y
authors.lastname: Wang
authors.forename: Qilong
authors.initials: Q
authors.lastname: Wang
authors.forename: Yingying
authors.initials: Y
authors.lastname: Li
authors.forename: Yinglan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xiao-lian
authors.initials: XL
authors.lastname: Zhang
mesh_terms: D000276:Adjuvants, Immunologic / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D000328:Adult; D000818:Animals; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000097:blood; D007378:Interleukins / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009132:Muscles / Q000382:microbiology / Q000473:pathology; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000502:physiology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D011817:Rabbits; D018123:Receptors, Interleukin / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D015398:Signal Transduction; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology / Q000628:therapy*; D000099180:Interleukin-24
chemical_list: D000276:Adjuvants, Immunologic; D007371:Interferon-gamma; D007378:Interleukins; D018123:Receptors, Interleukin; D011993:Recombinant Fusion Proteins; D000099180:Interleukin-24