INBIOMED   24026
INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Impaired migration of CD8+ T cells and poor parasite control in target tissues of IL-10 deficient mice during acute Trypanosoma cruzi infection
Autor/es:
BATALLA, ESTELA; ALBA SOTO, CATALINA; MIRANDA, CRISTIAN GABRIEL ; GULIN, ERNESTO ; PINO MARTÍNEZ, AGUSTINA ; GONZÁLEZ CAPPA, STELLA MARIS
Lugar:
Mar del Plata
Reunión:
Congreso; XXXI Reunión de la Sociedad Argentina de Protozoología; 2019
Institución organizadora:
SAIC-SAFE-SAB-SAP-AACYTAL-NANOMEDar-HCS
Resumen:
CD8+ T cells play a critical role limiting T. cruzi multiplication in peripheral tissues. To achieve this, they need to become functionally activated in lymphoid organs and sense environmental signals produced at the sites of inflammation to migrate, target and eliminate cells infected with intracellular amastigotes. We have previously established that IL-10 deficient mice (IL-10 KO) are more susceptible to infection with T. cruzi. Our findings demonstrated that splenic CD8+ T cells from IL-10 KO infected mice fail to expand and to become fully activated thus suggesting an immunostimulatory role of this cytokine during acute T. cruzi infection. We hypothesize that impairment in CD8+ T cell activation has consequences on their migration and function in target tissues. Here, we analyzed the effects of absence of IL-10 in hearts of T. cruzi mice and particularly, we analyzed histological changes, tissue infiltrates, parasite load as well as chemokines and chemokine receptors involved in migration of CD8+ T cells.After 21 days of infection tissue sections of hearts from IL-10 KO mice exhibited a higher score of diffuse and perivascular infiltrates than WT mice. The mRNA expression of chemokines CXCL9 and CXCL10 was upregulated in heart tissues of WT and IL-10 KO infected mice but to a greater extent in the last group correlating with their higher tissue inflammation. The mRNA expression of CXCR3- receptor of the aforementioned chemokines- in heart tissues was upregulated in the WT mice but not in KO mice. Moreover, CXCR3 expression by splenic CD8+T cells was upregulated in infected WT mice but did nor increase in IL-10 KO mice. The relative number of tissue infiltrating CD8+ T cells was increased upon infection in hearts of WT mice but not in IL-10 KO mice. Consistently, parasite burden in infected hearts was significantly lower in WT mice compared to their IL-10 KO counterparts.Together, this results show that IL-10 participates in events that lead to homing of CD8+ T cells to target tissues. Even tough lack of IL-10 increases target tissue inflammation and boosters the CXL9/CXL10 chemokine gradient, CD8+ T cells at lymphoid organs fail to increase expression of the chemokine receptor CXCR3 thus failing to migrate to inflamed tissues. The lower recruitment of CD8+ T cells in heart tissues finally leads to poor parasite control of IL-10 KO mice.