In vivo infection by Trypanosoma cruzi: the conserved FLY domain of the gp85/trans-sialidase family potentiates host infection.

Trypanosoma cruzi is a protozoan parasite that infects vertebrates, causing in humans a pathological condition known as Chagas' disease. The infection of host cells by T. cruzi involves a vast collection of molecules, including a family of 85 kDa GPI-anchored glycoproteins belonging to the gp85/trans-sialidase superfamily, which contains a conserved cell-binding sequence (VTVXNVFLYNR) known as FLY, for short. Herein, it is shown that BALB/c mice administered with a single dose (1 µg/animal, intraperitoneally) of FLY-synthetic peptide are more susceptible to infection by T. cruzi, with increased systemic parasitaemia (2-fold) and mortality. Higher tissue parasitism was observed in bladder (7·6-fold), heart (3-fold) and small intestine (3·6-fold). Moreover, an intense inflammatory response and increment of CD4+ T cells (1·7-fold) were detected in the heart of FLY-primed and infected animals, with a 5-fold relative increase of CD4+CD25+FoxP3+ T (Treg) cells. Mice treated with anti-CD25 antibodies prior to infection, showed a decrease in parasitaemia in the FLY model employed. In conclusion, the results suggest that FLY facilitates in vivo infection by T. cruzi and concurs with other factors to improve parasite survival to such an extent that might influence the progression of pathology in Chagas' disease.

Interference of natural mouse hepatitis virus infection with cytokine production and susceptibility to Trypanosoma cruzi.

Mouse hepatitis virus (MHV) infection can have a pronounced impact on several investigation areas. Reports on natural MHV outbreaks are rare and most studies have been conducted by deliberately infecting mice with MHV laboratory strains that cause moderate to severe disturbances to the immune system. We have investigated the effects of a natural acute outbreak of MHV in our otherwise specific-pathogen-free (SPF) inbred mouse colonies, and of enzootic chronic MHV infection on cytokine production and resistance to the intracellular pathogen Trypanosoma cruzi. We found that BALB/c and/or C57BL/6 SPF mice that had been injected with T. cruzi blood trypomastigotes from recently MHV-contaminated (MHV+) mice developed significantly higher parasite blood counts, accelerated death, and showed higher IL-10 production by spleen cells than their counterparts whose T. cruzi inoculum was derived from MHV-negative (MHV-) donors. Interferon-gamma (IFN-gamma) production by MHV+ and MHV- mice was not significantly different. In contrast, T. cruzi infection of chronically MHV-infected mice did not result in major changes in the course of infection when compared with that observed in mice from MHV- colonies, although a trend to higher parasitaemia levels was observed in BALB/c MHV+ mice. Nevertheless, both BALB/c and C57BL/6 T. cruzi-infected MHV+ mice had diminished IFN-gamma production to parasite-antigen stimulation in comparison with similarly infected MHV- mice. Interleukin-10 (IL-10) production levels by spleen cells did not differ between chronic MHV+ and MHV- mice, but IFN-gamma neutralization by monoclonal antibody treatment of anti-CD3-stimulated spleen cell cultures showed higher levels of IL-10 synthesis in MHV+ BALB/c mice.