Respuesta TH22 durante la tuberculosis pulmonar activa

IMPERIALE BR

Jornada; Webinar de TB; 2022

Hospital MUñiz

The role of interleukin-22 (IL-22) in the pathogenesis or tissue repair inhuman tuberculosis (TB) remains to be established. Here, we aimed toexplore the ex-vivo and in-vitro T helper 22 (Th22) response in TB patientsand healthy donors (HD) induced by different local multi-drug-resistant(MDR) Mvcobacterium tuberculosis (Mtb) strains. For this purpose, peripheralblood mononuclear cells from drug-susceptible (S-TB) MDR-TBpatients and HD were stimulated with local MDR strains and the laboratorystrain H37Rv. IL-22 and IL-17 expression and senescent status wereassessed in CD4+ and CD8+ cells by flow cytometry, while IL-22 amountwas measured in plasma and culture supernatants by enzyme-linked immunosorbentassay (ELISA). We found lower IL-22 amounts in plasmafrom TB patients than HD, together with a decrease in the number ofcirculating T cells expressing IL-22. In a similar manner, all Mtb strainsenhanced IL-22 secretion and expanded IL-22+ cells within CD4+ andCD8+ subsets, being the highest levels detected in S-TB patients. In MDRTB,low systemic and Mtb-induced Th22 responses associated with highsputum bacillary load and bilateralism of lung lesions, suggesting thatTh22 response could be influencing the ability of MDR-TB patients tocontrol bacillary growth and tissue damage. In addition, in MDR-TB patientswe observed that the higher the percentage of IL-22+ cells, the lowerthe proportion of programmed cell death 1 (PD-1)+ or CD57+ T cells.Furthermore, the highest proportion of senescent T cells was associatedwith severe lung lesions and bacillary load. Thus, T cell senescence wouldmarkedly influence Th22 response mounted by MDR-TB patients.