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

IMPERIALE, BELÉN R.; GAMBERALE, ANA; YOKOBORI, NOEMÍ; GARCÍA, ANA; BARTOLETTI, BRUNO; AIDAR, OMAR; LÓPEZ, BEATRIZ; CRUZ, VICTOR; GONZÁLEZ MONTANER, PABLO; PALMERO, DOMINGO J.; DE LA BARRERA, SILVIA

IMMUNOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Año: 2023

0019-2805

We previously reported that patients with multidrug-resistant tuberculosis (MDR-TB)showed low systemic and Mtb-induced Th22 responses associated to high sputumbacillary load and severe lung lesions suggesting that Th22 response could influencethe ability of these patients to control bacillary growth and tissue damage. In MDRTB patients, the percentage of IL-22+ cells inversely correlates with the proportion ofsenescent PD-1+ T cells. Herein, we aimed to evaluate the pathways involved on theregulation of systemic and Mtb-induced Th22 response in MDR-TB and fully drugsusceptible TB patients (S-TB) and healthy donors. Our results show that while IL-1βand IL-23 promote Mtb-induced IL-22 secretion and expansion of IL-22+ cells, TGF-βinhibits 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 andblockade of PD-1/PD-L1 signalling enhances in vitro Mtb-induced expansion of IL22+ cells. Thus, TGF-β could also inhibit Th22 response through upregulation of PD-1expression in T cells. Higher percentage of IL-23+ monocytes was observed in TBpatients. In contrast, the proportion of IL-1β+ monocytes was lower in TB patientswith bilateral lung cavities (BCC) compared to those patients with unilateral cavities(UCC). Interestingly, TB patients with BCC showed higher plasmatic and Mtbinduced TGF-β secretion than patients with UCC. Thus, high TGF-β secretion andsubtle differences in IL-23 and IL-1β expression could diminish systemic and in vitroMtb-induced Th22 response along disease progression in TB patients.