The role of small Heat Shock Proteins in Trypanosoma cruzi infection and intestinal homeostasis in a Chagas disease vector.

Rhodnius prolixus, an insect vector of Chagas disease, ingests blood meals several-fold its own body weight. This nutritional overload triggers specific adaptive responses that prevent or remediate damage from multiple stressors, including oxidative, osmotic, and microbial challenges. Transcriptomic analysis of first-instar nymph digestive apparatus revealed five members of the small Heat Shock Protein (sHSP) family that were highly expressed after blood meals but were downregulated upon Trypanosoma cruzi infection. sHSPs are proteins involved in cellular homeostasis and stress responses. Simultaneous knockdown of all five sHSPs profoundly disrupted insect physiology, causing decreased actin filament network formation, interrupted peristalsis, blocked endoplasmic reticulum (ER) expansion, and reduced ER-mitochondria association, while increasing reactive oxygen species generation and inducing premature epithelial cell mitosis. This apparent loss of digestive apparatus homeostasis was recapitulated by trypanosome infection and, conversely, sHSPs silencing in infected insects increased parasite numbers. Taken together, our data reveal a paramount role for sHSPs in midgut cell homeostasis following blood meals and support the hypothesis that sHSPs expression down regulation represents an adaptive manipulation of the insect host by the parasite.