title: Tuberculosis antigen-induced expression of IFN-α in tuberculosis patients inhibits production of IL-1β.
abstract: The mechanism by which IFN-α regulates the host response to Mycobacterium tuberculosis (M.tb) infection in humans is poorly understood. In the present study, we found that freshly isolated pleural fluid mononuclear cells (PFMCs) from tuberculous pleural effusion but not peripheral blood mononuclear cells (PBMCs) spontaneously expressed IFN-α and IL-1β in vivo. In addition, exogenous IFN-α significantly inhibited production of IL-1β in PFMCs after stimulation with Bacillus Calmette-Guérin (BCG). To further evaluate the effect of endogenous IFN-α on BCG-induced IL-1β production, a neutralizing antibody to IFN-α was added to the cultures of BCG-stimulated PFMCs. As expected, neutralization of IFN-α by antibody significantly enhanced the production of IL-1β. Notably, we showed that IFN-α inhibited production of IL-1β through 2 distinct mechanisms: IFN-α signaling, via the STAT1 transcription factor, suppressed caspase-1-dependent IL-1β maturation, and IFN-α induced the production of IL-10 in a STAT1-dependent manner in which IL-10 reduced the abundance of IL-1β. In contrast, we found that IFN-α enhanced the production of IFN-γ, and IFN-γ also suppressed IL-1β production in the PFMCs during BCG stimulation. Our findings demonstrate that IFN-α employs distinct pathways for regulating IL-1β production and reveal that in the case of M.tb infection, the induction of IFN-α and IFN-γ might be associated with M.tb immune escape and disease progression in infected humans.-Ma, J., Yang, B., Yu, S., Zhang, Y., Zhang, X., Lao, S., Chen, X., Li, B., Wu, C. Tuberculosis antigen-induced expression of IFN-α in tuberculosis patients inhibits production of IL-1β.
authors.affiliation: Institute of Immunology, Zhongshan School of Medicine; Key Laboratory of Tropical Disease Control Research of Ministry of Education, Sun Yat-sen University, Guangzhou, China;
authors.forename: Jiangjun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Institute of Immunology, Zhongshan School of Medicine; Key Laboratory of Tropical Disease Control Research of Ministry of Education, Sun Yat-sen University, Guangzhou, China;
authors.forename: Binyan
authors.initials: B
authors.lastname: Yang
authors.affiliation: Institute of Immunology, Zhongshan School of Medicine; Key Laboratory of Tropical Disease Control Research of Ministry of Education, Sun Yat-sen University, Guangzhou, China;
authors.forename: Sifei
authors.initials: S
authors.lastname: Yu
authors.affiliation: Institute of Immunology, Zhongshan School of Medicine; Key Laboratory of Tropical Disease Control Research of Ministry of Education, Sun Yat-sen University, Guangzhou, China;
authors.forename: Yannan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Chest Hospital of Guangzhou, Guangzhou, China;
authors.forename: Xianlan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Chest Hospital of Guangzhou, Guangzhou, China;
authors.forename: Suihua
authors.initials: S
authors.lastname: Lao
authors.affiliation: Shenzhen Key Laboratory of Infection and Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, China; and.
authors.forename: Xinchun
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Immunology, Research Center of Immunology, Bengbu Medical College, Bengbu, China.
authors.forename: Baiqing
authors.initials: B
authors.lastname: Li
authors.affiliation: Institute of Immunology, Zhongshan School of Medicine; Key Laboratory of Tropical Disease Control Research of Ministry of Education, Sun Yat-sen University, Guangzhou, China; changyou_wu@yahoo.com.
authors.forename: Changyou
authors.initials: C
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology*; D020170:Caspase 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009163:Mycobacterium bovis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D016898:Interferon-alpha; D053583:Interleukin-1beta; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D016753:Interleukin-10; D007371:Interferon-gamma; D020170:Caspase 1
keywords: BCG; PFMCs; TB-Ag