Correlação entre a expressão de receptores da resposta imune inata e as formas clínicas na doença de Chagas humana

Abstract

Recent studies have established the importance of Toll Like Receptors (TLRs) and Nod Like Receptors (NLRs) in resistance for Trypanosoma cruzi infection in experimental models. However, there are not studies correlating the expression of these molecules to clinical forms of chronic human Chagas disease. In this study, we aim to evaluate the expression of innate immunity receptors (Toll and Nod), signaling molecules, cytokines and -defensins in patients with chronic Chagas disease that displayed indeterminate (n=18), cardiac (n=17), digestive (n=9) and cardiodigestive (n=10) clinical forms. Uninfected individuals from the same geographical region were used as control (n=9). The quantification of mRNA expression was performed by real-time PCR, from peripheral blood mononuclear cells (PBMC), TLRs (TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9), NLRs (NOD1 and NOD2), the adapter molecules RIP2 (Receptor-interacting protein kinase 2), TRIF (Toll/IL-1 Receptor Domain-Containing Adaptor-Inducing IFN-), Myd88 (Myeloid Differentiation Primary Response Gene 88), cytokines (IL-1, IL-6, IL-12, IL-18 and IFN-) and -defensins (5 and 6). There was no difference in the expression of mRNA for TLRs (TLR1, 2, 3, 4, 5, 6, 7 and 9) and the adapter molecule TRIF between patients presenting different clinical forms of Chagas disease. However, patients with cardiodigestive form displayed highest expression of TLR8 and Myd88 mRNA compared to cardiac and indeterminate clinical forms. Patients with cardiac form showed higher mRNA expression of IL-1 and IL12, which is associated with the development of severe cardiac disease. Furthermore, there was no difference between the expression of other cytokines analyzed (IL-6, IL-18 and IFN-). Patients with digestive form of the disease showed lower expression of NOD2 and higher expression of RIP2 compared with indeterminate form. Also, there was a negative correlation between the expression of NOD2 and the degree of dilation of the esophagus (R=-0.7859, p=0.0172) and sigmoid (R=-0.7859, p=0, 0172). Patients with digestive form showed higher expression of -defensin 6. The results indicate that high mRNA expression of IL1- and IL-12 is correlated to chronic Chagas cardiomyopathy, and the absence or low NOD2 mRNA expression is correlated with the severity of digestive clinical form of Chagas disease.