Incomplete recruitment of protective T cells facilitates Trypanosoma cruzi persistence in the mouse colon

Abstract

Trypanosoma cruzi is the etiological agent of Chagas disease. Following T cell mediated suppression of the acute phase infection, this intracellular eukaryotic pathogen persists in a limited sub-set of tissues at extremely low-levels. The reasons for this tissue-specific chronicity are not understood. Using a dual bioluminescent:fluorescent reporter strain, which allows experimental infections to be imaged at single-cell resolution, we have characterised the hyper-local immunological microenvironment of rare parasitized cells in the mouse colon, a key site of persistence. We demonstrate that incomplete recruitment of T cells to infection foci permits the occurrence of repeated cycles of intracellular parasite replication and differentiation to motile trypomastigotes at a frequency sufficient to perpetuate chronic infections. The life-long persistence of parasites in this tissue site continues despite the presence, at a systemic level, of a highly effective T cell response. Overcoming this low-level dynamic host:parasite equilibrium represents a major challenge for vaccine development.