Effects of Type II Diabetes Mellitus on the Immune Response to Trypanosoma Cruzi Experimental Infection

MAZZOCCO, YANINA; BERGERO, GASTÓN; DEL ROSSO, SEBASTIAN; BAIGORRI, ELIANA; MLADIN, JUAN; MARTINEZ, CLAUDIA; RODRIGUEZ GALÁN, MARÍA CECILIA; CANO, ROXANA; AOKI, MARIA DEL PILAR

San Luis

Congreso; Reunión Anual de la Sociedad Argentina de Inmunología; 2023

Sociedad Argentina de Inmunología

Introduction and Objectives: Given the increased susceptibility to infections associated with type 2 diabetes mellitus (T2DM), the purpose of the present work was to determine the effects of T2DM on a mouse model of Trypanosoma (T.) cruzi infection. Materials and Methods: To this aim, 8-week-old C57BL/6 mice were fed a medium-fat diet (17% FAT) combined with 20% fructose in drinking water for 20 weeks. At week 8, a single dose of the diabetogenic drug streptozotocin (100 mg/kg) was injected (i.p.) to establish diabetes (D+T). In this group, the glycemia significantly increased compared to those who had not received either the diet or the drug (p=0,01). Diabetic (D+Ti) and non-diabetic (Ni) mice were infected with 1000 T. cruzi trypomastigotes (i.p.). Results: We found that D+T animals had higher plasma IL-10 concentrations than nondiabetic controls (p= 0,02). At 14 days post-infection, the D+Ti group showed greater parasitemia (p=0,03) and plasmatic concentrations of IL-6 (p=0,01), as well as inflammatory cytokines such as IL-1α (p=0,01), TNF-α (p=0,01), IL-12p70 (P=0,03), and the chemokines MCP-1 (p=0,01) or GM-CSF (p=0,02) than the Ni group. In addition, D+Ti had a higher frequency of circulating CD11b+Ly6Chi cells (p= 0.03) and a lower frequency of Ly6Clo monocytes (p=0,01) than Ni. Notably, the Ly6Clo cells exhibited higher IL-10 expression (p=0,02) in D+Ti than Ni. Moreover, the D+Ti group showed a lower frequency of circulating granzyme B+ (p= 0,01) and perforin+ (p= 0,01) CD8 T-cells. In the spleen, the frequency of granzymes B+ CD8 T-cells (p= 0,02) and the frequency and total number of effector memory T cells (CD44+CD49d+) (P%=0,01; P#= 0,01) were lower in the group D+Ti than in the Ni. In agreement, the production of TNF-α by CD8 T-cells was lower in D+Ti than in Ni (PMFI= 0,03; P%=0,01). Surprisingly, D+Ti animals showed a lower frequency of macrophages (CD45+CD11b+F4/80+) in VAT than Ni mice (p=0,01), and the M1-like population (CD86+) showed a lower frequency of TNF-α expression (p=0,03). Conclusion: Our results suggest a blunted immune response to T. cruzi infection in a novel murine T2DM model. In particular, the observed imbalance in inflammatory cytokines and reduced CD8+ T-cell effector molecules highlight the impaired immunocompetence at several immune compartments to deal with infections in T2DM.