Th22 response induced byMycobacterium tuberculosisstrains is closely related to severity of pulmonary lesions and bacillary load in patients with multi-drug-resistant tuberculosis

Abstract

Summary The role of interleukin-22 (IL-22) in the pathogenesis or tissue repair in human tuberculosis (TB) remains to be established. Here, we aimed to explore the ex-vivo and in-vitro T helper 22 (Th22) response in TB patients and healthy donors (HD) induced by different local multi-drug-resistant (MDR) Mvcobacterium tuberculosis (Mtb) strains. For this purpose, peripheral blood mononuclear cells from drug-susceptible (S-TB) MDR-TB patients and HD were stimulated with local MDR strains and the laboratory strain H37Rv. IL-22 and IL-17 expression and senescent status were assessed in CD4+ and CD8+ cells by flow cytometry, while IL-22 amount was measured in plasma and culture supernatants by enzyme-linked immunosorbent assay (ELISA). We found lower IL-22 amounts in plasma from TB patients than HD, together with a decrease in the number of circulating T cells expressing IL-22. In a similar manner, all Mtb strains enhanced IL-22 secretion and expanded IL-22+ cells within CD4+ and CD8+ subsets, being the highest levels detected in S-TB patients. In MDR-TB, low systemic and Mtb-induced Th22 responses associated with high sputum bacillary load and bilateralism of lung lesions, suggesting that Th22 response could be influencing the ability of MDR-TB patients to control bacillary growth and tissue damage. In addition, in MDR-TB patients we observed that the higher the percentage of IL-22+ cells, the lower the proportion of programmed cell death 1 (PD-1)+ or CD57+ T cells. Furthermore, the highest proportion of senescent T cells was associated with severe lung lesions and bacillary load. Thus, T cell senescence would markedly influence Th22 response mounted by MDR-TB patients.

Characterization of Mycobacterium tuberculosis–Specific Th22 Cells and the Effect of Tuberculosis Disease and HIV Coinfection

“…Of note, group 1 CD1-restricted T cells specific for microbial lipid Ags display similar ab TCR usage to peptide-specific T cells (57). A further possibility, given the demonstrated role of Th22 in HN878 infection (17), is that Th22 cells respond to peptides overrepresented in particular clinical strains or lineages, including drugresistant isolates (58).…”

Microsporum gypseum Isolated from Ailuropoda melanoleuca Provokes Inflammation and Triggers Th17 Adaptive Immunity Response

“…IL-22 produced by Th22 cells is involved in protecting mucosal surfaces from tissue damage. It simultaneously synergizes with IL-17A and IL-17F to induce antimicrobial peptide expression in epithelial cells and mediate an early mucosal defense response to pneumonia-causing microorganisms in a mouse model [ 47 , 48 ]. Here, IL-22 expression was significantly upregulated in lung tissue at 2 and 5 dpi.…”

Current Knowledge of Th22 Cell and IL-22 Functions in Infectious Diseases

“…Mycobacterium tuberculosis (MTB) is a common pathogen that is primarily transmitted via the respiratory tract [ 128 ]. Compared to healthy controls, TB patients had lower levels of IL-22 and IL-22 + T cells in their plasma [ 129 , 130 ]. Th22 cells are the main IL-22 producers during MTB infection, but other subsets, such as Th1 cells, CD8+ T cells, and NKT cells, also secrete IL-22 [ 131 , 132 , 133 ].…”

“…IL-22 is also involved in the formation of protective lymphoid follicular structures, called inducible bronchus-associated lymphoid tissues (iBALT), through the CXCR5–CXCL13 axis [ 139 ]. In patients infected with multidrug-resistant MTB (MDR-TB) , decreased Th22 cell responses are associated with high sputum bacterial loads and severe lung lesions, suggesting that Th22 cells influence the antimicrobial capacity of TB patients [ 129 ]. Moreover, fewer T cells that release PD-1 or CD57 were found in multidrug-resistant TB patients with high levels of Th22 cells [ 129 ].…”