IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Th22 response induced by Mycobacterium tuberculosis strains in patients with multidrug-resistant tuberculosis
Autor/es:
MINOTTI ALAN; PALMERO DOMINGO; DE LA BARRERA SILVIA; IMPERIALE BELÉN; GONZALEZ MONTANER PABLO; MORCILLO NORA; GARCÍA ANA; MORACHO LUCILA
Lugar:
Buenos Aires
Reunión:
Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2020; 2020
Institución organizadora:
Sociedad Argentina de Inmunología Clínica, Sociedad Argentina de Inmunología y Sociedad Argentina de Fisiología
Resumen:
Tuberculosis (TB) remains a major global health problem and is the second leading cause of death from infectious diseases worldwide. Regarding TB immunity, the most important response has been attributed to T cells, with CD4+ T cells playing a crucial role both forthe control of infection and the tissue damage. And, although TH1 lymphocytes are essential to control TB infection, other lymphocytes, such as TH22, would participate in this response. IL-22 acts on the mucous membrane promoting tissue repair or inflammatory processes. During TB, CD4+ T cells can evolve to effector cells with membrane-bound IL-22 (Mb-IL-22) inhibiting M. tuberculosis (Mtb) replication into macrophages. Besides, the genetic variability of Mtb could influence immune response. The aim of the study was to explore the TH22 response induced by different Mtb strains during active pulmonary TB. Peripheral blood samples were obtained from patients with multidrug-resistant TB (MDR-TB, n: 59), drug-susceptible TB (S-TB, n: 27) and healthy donors (HD, n: 20). Peripheral blood mononuclear cells (PBMCs) were isolated and cultured alone or with γ-irradiated Mtb strains. IL-22 secretion was measured from plasma and culture supernatants by ELISA while intracellular IL-22 (ic-IL-22) and Mb-IL-22 levels as well as senescent T cells markers, CD57 and PD-1, were determined by flow cytometry. IL-22 T cells expression was higher in S-TB than in MDR-TB and HD despitethe strain employed as antigen. Plasma IL-22 levels in TB patients were lower than in HD. Besides, in MDR-TB patients, the greater the bacillary load and the severity of the lesion, the lower IL-22 expression in T cells and IL-22 secretion by stimulated PBMC. In addition, CD57+ and PD1+ T cells were markedly increased in MDR-TB patients and inversely correlated with IL-22 expression, reflecting that T cell exhaustion could lead to a deficient of the host to mount adequate TH22 responses, decrease bacterial load and mount tissue repair mechanisms.