Salivary shield: Rhodnius prolixus salivary glandular extract reduces intestinal immunopathology and protects against Toxoplasma gondii infection

Abstract

C57BL/6 mice, orally infected with T. gondii, experience pronounced severe intestinal inflammation, causing necrosis, weight loss, and bacterial translocation. In addition, immunomodulatory molecules such as lipocalins, nitrophorins, and apyrases are present in R. prolixus saliva. Our objective was to assess the immunomodulatory effects of the salivary gland extract (SGE) of R. prolixus in mice orally infected by T. gondii. Experimental groups received no treatment (PBS) or SGE (10 µg and 30 µg) in the chronic infection phase and (30 µg) in the acute infection phase. Control groups were non-infected and treated or not treated with SGE (30 µg). SGE was injected intraperitoneally daily, and mice were infected by gavage with 20 cysts of T. gondii (ME-49 strain) on the third treatment day. The treatment duration for the experiment was 23 days for the chronic infection phase (corresponding to 20 days of infection) and 12 days for the acute infection phase (corresponding to 9 days of infection). SGE-treated mice showed reduced small intestine shortening, weight loss, clinical scores, and higher survival rates. Treated mice also exhibited increased secretion of regulatory and protective cytokines (IL-4, IL-2, IL-10, IL-22) and higher levels of IL-4 (chronic phase), IL-2, and IL-22 (acute phase) in the gut. SGE treatment (30 µg) demonstrated protective effects in both the duodenum and ileum of T. gondii-infected mice. Treated animals showed better-preserved villus architecture, increased goblet and Paneth cell counts, and shallower crypts. Correlation data revealed that treated animals exhibited a more regulated and protective immune response. Overall, SGE contributed to the preservation of intestinal integrity and the reduction of inflammation. Thus, we conclude that SGE induces a regulatory response, mitigating inflammation and protecting against T. gondii infection.