Estatus inmunológico de las madres infectadas por T. cruzi / Immunological status of mothers infected with Trypanosoma cruzi

The mechanisms of congenital transmission of Chagas disease remain largely unknown. To better understand the role of maternal immunology during pregnancy in congenital Chagas transmission, we studied the cytokine production and the parasitic load in three groups of mothers: infected mothers who transmitted the disease to their babies (M+B+-), infected mothers who did not transmit the disease to their babies (M+B-) and not infected mothers as a control group (M-B-). M+B+ mothers produced less IFNgamma and more IL-10 than the M+B- mothers, and they are not able to produce IL-2. M+B+ mothers showed a higher parasitic load. These results, indicated that the congenital Chagas transmission is associated with an immunological imbalance and a high parasitic load in the M+B+ mothers.

Respuesta inmune en neonatos no infectados nacidos de madres infectadas por Trypanosoma cruzi / Immune responses of non-infected neonates of mothers infected with Trypanosoma cruzi

We have investigated if maternal T. cruzi infection could induce in utero innate and/or adaptive immune responses in uninfected neonates by measuring specific IgM and IgA antibodies in cord blood plasma, and by performing phenotypic and functional studies of umbilical cord blood cells of their newborns (M+B- group). We detected T. cruzi-specific IgM and IgA antibodies in M+B- cord blood, indicating they had mounted in utero a strong B cell response, although they are not infected. On the other hand, circulating T cells of such uninfected neonates displayed a low level of activation, as seen bya slightly increased expression of the activation markers CD45RO on CD4+ T cells and HLA-DR on CD8+ T cells, although the proportion of CD4+ and CD8+ T cells was unmodified as compared to newborns from uninfected mothers (MB- group). This activation did not give rise to a proliferative response upon stimulation by T. cruzi antigens in vitro. However, M+B- cells produced low levels of lymphokines (IFN-gamma and IL-13) upon mitogenic stimulation, which was not the case of M-B- newborn cells. Beside this, M+B- blood cells produced higher levels of inflammatory cytokines (IL-1b, IL-6, TNF-alpha) than M-B- cells when stimulated with the T. cruzi lysate or LPS, suggesting the over-activation of the innate response in M+B- newborns. Monocytes participated in such inflammatory response since M+B- purified cord blood monocytes produced higher levels of TNF- when incubated with LPS or a T. cruzi lysate than M-B- cells. Altogether, these results show that, even in the absence of congenital infection, maternal T. cruzi infection triggers in utero both adaptive and innate immune responses in their babies. This indicates that parasite circulating antigens have been transferred from mothers to their fetuses.