Transforming growth factor- β, Interleukin-23 and interleukin-1β modulate TH22 response during active multidrug-resistant tuberculosis

Immunology. 2023 Sep 16. doi: 10.1111/imm.13698. Online ahead of print.ABSTRACTWe previously reported that patients with multidrug-resistant tuberculosis (MDR-TB) showed low systemic and Mtb-induced Th22 responses associated to high sputum bacillary load and severe lung lesions suggesting that Th22 response could influence the ability of these patients to control bacillary growth and tissue damage. In MDR-TB patients, the percentage of IL-22+ cells inversely correlates with the proportion of senescent PD-1+ T cells. Herein, we aimed to evaluate the pathways involved on the regulation of systemic and Mtb-induced Th22 response in MDR-TB and fully drug-susceptible TB patients (S-TB) and healthy donors. Our results show that while IL-1β and IL-23 promote Mtb-induced IL-22 secretion and expansion of IL-22+ cells, TGF-β inhibits this response. Systemic and in vitro Mtb-induced Th22 response inversely correlates with TGF-β amounts in plasma and in PBMC cultures respectively. The number of circulating PD-1+ T cells directly correlates with plasmatic TGF-β levels and blockade of PD-1/PD-L1 signalling enhances in vitro Mtb-induced expansion of IL-22+ cells. Thus, TGF-β could also inhibit Th22 response through upregulation of PD-1 expression in T cells. Higher percentage of IL-23+ monocytes was observed in TB patients. In contrast, the proportion of IL-1β+ monocytes was lower in TB patients with bilateral lung cavities (BCC) compared to those patients with unilateral cavities (UCC...
Source: Immunology - Category: Allergy & Immunology Authors: Source Type: research