The regulation and potential role of interleukin-32 in tuberculous pleural effusion

Front Immunol. 2024 May 13:15:1342641. doi: 10.3389/fimmu.2024.1342641. eCollection 2024.

Abstract

The possible protective effect of interleukin-32 (IL-32) in Mycobacterium tuberculosis (Mtb) infection has been indicated. However, few studies have been focused on IL-32 in tuberculosis patients. Additionally, the regulation of IL-32 production has rarely been reported. In the present study, the production, regulation, and role of IL-32 in tuberculous pleurisy (TBP) were investigated. We found that the content of IL-32 in tuberculous pleural effusion (TPE) was higher than the level in the malignant pleural effusion and transudative pleural effusion. The level of IL-32 mRNA in pleural fluid mononuclear cells (PFMCs) was higher than that in peripheral blood mononuclear cells (PBMCs) of patients with TBP, and this difference was mainly reflected in the splice variants of IL-32α, IL-32β, and IL-32γ. Compared with the PBMCs, PFMCs featured higher IL-32β/IL-32γ and IL-32α/IL-32γ ratios. In addition, lipopolysaccharide (LPS), Bacillus Calmette-Guérin (BCG), and H37Ra stimulation could induce IL-32 production in the PFMCs. IL-32 production was positively correlated with the TNF-α, IFN-γ, and IL-1Ra levels in TPE, whereas IFN-γ, but not TNF-α or IL-1Ra, could induce the production of IL-32 in PFMCs. Furthermore, IL-32γ could induce the TNF-α production in PFMCs. Monocytes and macrophages were the main sources of IL-32 in PFMCs. Nevertheless, direct cell-cell contact between lymphocytes and monocytes/macrophages plays an important role in enhancing IL-32 production by monocyte/macrophage cells. Finally, compared with the non-tuberculous pleural effusion, the purified CD4+ and CD8+ T cells in TPE expressed higher levels of intracellular IL-32. Our results suggested that, as a potential biomarker, IL-32 may play an essential role in the protection against Mtb infection in patients with TBP. However, further studies need to be carried out to clarify the functions and mechanisms of the IFN-γ/IL-32/TNF-α axis in patients with TBP.

Keywords: IFN-γ; IL-32; immune; tuberculosis; tuberculous pleural effusion (TPE).

MeSH terms

  • Adult
  • Aged
  • Female
  • Humans
  • Interferon-gamma / metabolism
  • Interleukins* / immunology
  • Interleukins* / metabolism
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology
  • Pleural Effusion* / immunology
  • Pleural Effusion* / metabolism
  • Pleural Effusion* / microbiology
  • Tuberculosis, Pleural* / immunology
  • Tuberculosis, Pleural* / metabolism

Substances

  • IL32 protein, human
  • Interleukins
  • Interferon-gamma

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by the Basic Applied Research Project of Wuhan Science and Technology Bureau (No. 2023020201010215 to XW), the Foundation of Wuhan Pulmonary Hospital (No. YNZZ202204 to XW). This research was also supported by the National Natural Science Foundation of China (No. 82200015 to PL), the Basic Applied Research Project of Wuhan Science and Technology Bureau (No: 2023020201010214 to PL), the Science and Technology Project of Shenzhen (No. JCYJ20220530163216036 to PL).