The immune characterization of interferon-β responses in tuberculosis patients

Microbiol Immunol. 2018 Apr;62(4):281-290. doi: 10.1111/1348-0421.12583. Epub 2018 Apr 18.

Abstract

We aimed to assess the immunoregulatory effects of IFN-β in patients with tuberculous pleurisy. IFN-β, IFN-γ and IL-17 expression levels were detected, and correlations among these factors in different culture groups were analyzed. Pleural fluid mononuclear cells (PFMC) from tuberculous pleural effusions, but not peripheral blood mononuclear cells (PBMC) from healthy donors, spontaneously expressed IFN-β, IL-17 and IFN-γ. Moreover, exogenous IFN-β significantly inhibited the expression of IL-17 in PFMC. By contrast, IFN-β simultaneously enhanced the levels of IFN-γ. To further investigate the regulation of IL-17 and IFN-γ by endogenous IFN-β, an IFN-β neutralizing antibody was simultaneously added to bacillus Calmette-Guérin (BCG)-stimulated PFMC. IL-17 expression was significantly increased, but IFN-γ production was markedly decreased in the experimental group supplemented with the IFN-β neutralizing antibody. Simultaneously, IL-17 production was remarkably increased in the experimental group supplemented with the IFN-γ neutralizing antibody. Taken together, in our study, we first found that freshly isolated PFMC, but not PBMC from healthy donors, spontaneously expressed IFN-β, IL-17 and IFN-γ in vivo. Moreover, IFN-β suppressed IL-17 expression and increased IFN-γ production. Furthermore, both IFN-β and IFN-γ down-regulated IL-17 expression. These observations suggest that caution is required when basing anti-tuberculosis treatment on the inhibition of IFN-β signaling.

Keywords: IFN-β; bacillus Calmette-Guérin (BCG); pleural fluid mononuclear cell (PFMC).

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Neutralizing
  • Antigens, Bacterial / immunology
  • Cytokines / blood
  • Cytokines / genetics
  • Cytokines / immunology
  • Cytokines / metabolism
  • Female
  • Gene Expression
  • Humans
  • Interferon-beta / biosynthesis*
  • Interferon-beta / blood
  • Interferon-beta / genetics
  • Interferon-beta / immunology*
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / blood
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology*
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / blood
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology*
  • Leukocytes, Mononuclear / immunology
  • Lipopolysaccharide Receptors
  • Male
  • Middle Aged
  • Mycobacterium bovis / immunology
  • Mycobacterium tuberculosis / immunology
  • Pleural Effusion / immunology
  • Th1 Cells
  • Th17 Cells
  • Tuberculosis / immunology*
  • Young Adult

Substances

  • Antibodies, Neutralizing
  • Antigens, Bacterial
  • Cytokines
  • IL17A protein, human
  • Interleukin-17
  • Lipopolysaccharide Receptors
  • Interferon-beta
  • Interferon-gamma