Enhanced immune response of MAIT cells in tuberculous pleural effusions depends on cytokine signaling

Jing Jiang; Xinchun Chen; Hongjuan An; Bingfen Yang; Fuping Zhang; Xiaoxing Cheng

doi:10.1038/srep32320

Enhanced immune response of MAIT cells in tuberculous pleural effusions depends on cytokine signaling

Sci Rep. 2016 Sep 2:6:32320. doi: 10.1038/srep32320.

Authors

Jing Jiang^{1

2

3}, Xinchun Chen^{1

4}, Hongjuan An², Bingfen Yang², Fuping Zhang³, Xiaoxing Cheng²

Affiliations

¹ Shenzhen Key Laboratory of Infection and Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, Guangdong, China.
² Division of Research, Institute of Tuberculosis, 309th Hospital, Beijing, China.
³ Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
⁴ Department of Pathogen Biology, School of Medicine, Shenzhen University, Shenzhen, Guangdong, China.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antibodies, Blocking / pharmacology
Female
Gene Expression Regulation
Granzymes / genetics
Granzymes / immunology
Humans
Immunity, Cellular*
Interferon-gamma / genetics
Interferon-gamma / immunology
Interleukin-12 / antagonists & inhibitors
Interleukin-12 / genetics
Interleukin-12 / immunology
Interleukin-12 Subunit p40 / genetics
Interleukin-12 Subunit p40 / immunology
Interleukin-17 / genetics
Interleukin-17 / immunology
Interleukin-18 / antagonists & inhibitors
Interleukin-18 / genetics
Interleukin-18 / immunology
Interleukin-2 / antagonists & inhibitors
Interleukin-2 / genetics
Interleukin-2 / immunology
Lipopolysaccharide Receptors / genetics
Lipopolysaccharide Receptors / immunology
Male
Mucosal-Associated Invariant T Cells / immunology*
Mucosal-Associated Invariant T Cells / microbiology
Mycobacterium tuberculosis / immunology*
Mycobacterium tuberculosis / pathogenicity
Pleural Effusion / immunology*
Pleural Effusion / microbiology
Pleural Effusion / pathology
Primary Cell Culture
Receptors, Antigen, T-Cell, gamma-delta / genetics
Receptors, Antigen, T-Cell, gamma-delta / immunology
Signal Transduction / immunology*
Tuberculosis, Pleural / immunology*
Tuberculosis, Pleural / microbiology
Tuberculosis, Pleural / pathology

Substances

Antibodies, Blocking
IL17F protein, human
IL18 protein, human
Interleukin-12 Subunit p40
Interleukin-17
Interleukin-18
Interleukin-2
Lipopolysaccharide Receptors
Receptors, Antigen, T-Cell, gamma-delta
Interleukin-12
Interferon-gamma
Granzymes