title: Enhanced immune response of MAIT cells in tuberculous pleural effusions depends on cytokine signaling.
abstract: The functions of MAIT cells at the site of Mycobacterium tuberculosis infection in humans are still largely unknown. In this study, the phenotypes and immune response of MAIT cells from tuberculous pleural effusions and peripheral blood were investigated. MAIT cells in tuberculous pleural effusions had greatly enhanced IFN-γ, IL-17F and granzyme B response compared with those in peripheral blood. The level of IFN-γ response in MAIT cells from tuberculous pleural effusions was inversely correlated with the extent of tuberculosis infection (p = 0.0006). To determine whether cytokines drive the immune responses of MAIT cells at the site of tuberculosis infection, the role of IL-1β, IL-2, IL-7, IL-12, IL-15 and IL-18 was investigated. Blockade of IL-2, IL-12 or IL-18 led to significantly reduced production of IFN-γ and/or granzyme B in MAIT cells from tuberculous pleural effusions. Majority of IL-2-producing cells (94.50%) in tuberculous pleural effusions had phenotype of CD3(+)CD4(+), and most IL-12p40-producing cells (91.39%) were CD14(+) cells. MAIT cells had significantly elevated expression of γc receptor which correlated with enhanced immune responses of MAIT cells. It is concluded that MAIT cells from tuberculous pleural effusions exhibited highly elevated immune response to Mtb antigens, which are controlled by cytokines produced by innate/adaptive immune cells.
authors: Shenzhen Key Laboratory of Infection and Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, Guangdong, China.|Division of Research, Institute of Tuberculosis, 309th Hospital, Beijing, China.|Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors: Jing
authors: J
authors: Jiang
authors: Shenzhen Key Laboratory of Infection and Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, Guangdong, China.|Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen, Guangdong, China.
authors: Xinchun
authors: X
authors: Chen
authors: Division of Research, Institute of Tuberculosis, 309th Hospital, Beijing, China.
authors: Hongjuan
authors: H
authors: An
authors: Division of Research, Institute of Tuberculosis, 309th Hospital, Beijing, China.
authors: Bingfen
authors: B
authors: Yang
authors: Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
authors: Fuping
authors: F
authors: Zhang
authors: Division of Research, Institute of Tuberculosis, 309th Hospital, Beijing, China.
authors: Xiaoxing
authors: X
authors: Cheng
mesh_terms: D000328:Adult; D019138:Antibodies, Blocking / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D053804:Granzymes / Q000235:genetics / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D053762:Interleukin-12 Subunit p40 / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D020382:Interleukin-18 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000276:immunology; D008297:Male; D000072336:Mucosal-Associated Invariant T Cells / Q000276:immunology* / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D010996:Pleural Effusion / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D061251:Primary Cell Culture; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D014396:Tuberculosis, Pleural / Q000276:immunology* / Q000382:microbiology / Q000473:pathology
chemical_list: D019138:Antibodies, Blocking; C440021:IL17F protein, human; C000589760:IL18 protein, human; D053762:Interleukin-12 Subunit p40; D020381:Interleukin-17; D020382:Interleukin-18; D007376:Interleukin-2; D018950:Lipopolysaccharide Receptors; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018664:Interleukin-12; D007371:Interferon-gamma; D053804:Granzymes