ImpactU Versión 3.11.2 Última actualización: Interfaz de Usuario: 16/10/2025 Base de Datos: 29/08/2025 Hecho en Colombia
Evaluación de la respuesta del TGF-beta y los linfocitos t residentes de memoria intestinales y esplénicos durante la infección por rotavirus en un modelo múrido
Rotavirus (RV) is one of the main causal agents of childhood acute gastroenteritis. In 2015, rotavirus infection generated 29.3% of all deaths from diarrhea in children under 5 years of age. The characteristics of the protective immune response induced against rotavirus are not known in detail. Two important immunological components are unknown: the role of transforming growth factor β (TGFβ) and resident memory T lymphocytes (LTrm). In the present work, these components were evaluated during rotavirus infection in mice. To meet our first objective, neonatal C57BL/6 mice were inoculated with mock (negative control) or with homologous (RV-EC) or heterologous (RRV) rotavirus. At days 2, 4, 6, 8, and 12 post-infection (PI) the mRNA levels of the TGFβ gene in the spleen and small intestine, and the protein levels of TGFβ1 in the intestinal content and serum were evaluated. The results suggest that neonatal mice infected with RRV and RV-EC show changes in the expression of tgfb1 mRNA and/or TGFβ1 protein at the systemic and intestinal level at different PI days. Our second objective sought to evaluate the frequency and phenotype of total and RV-specific intestinal memory resident T cells (LTrmi) and splenic T cells in RRV-infected mice. Initially, adult C57BL/6 mice were used to standardize the isolation and staining of LTrm from the spleen and small intestine. Subsequently, adult C57BL/6 mice were inoculated with 10_7 FFU of RRV or mock. At 7 days post-infection (DPI), intravascular (IV) staining was performed using an anti-CD45.2 antibody (marker present in all leukocytes), euthanasia was performed, and a blood sample, spleen, and small intestine were extracted. Cells extracted from these organs were stained with rotavirus-specific tetramer and surface markers and were analyzed by spectral cytometry. Thus, the phenotype and frequency of LTrms (total and RRV-specific) were described, and markers important for the development, regulation, and maintenance of this subset of T cells in adult control and infected with RRV mice were analyzed (spleen, lymphocytes lamina propria (LPL) and intraepithelial lymphocytes (IEL) from the small intestine). It was identified that at day 7 PI the IV (CD45.2+) CD8+ specific for RV T cells isolated from the spleen were probably activated in the intestine and showed a short-lived effector T cells (SLEC) phenotype, unlike non-IV (CD45.2-) resident T cells with a greater differentiation towards memory precursor T cells (MPEC). Our next objective, contemplated in a new ongoing project, is to evaluate the role of TGF-beta in the generation of LTrmi.