Annexin A1 is crucial during Toxoplasma gondii infection promoting the modulation of inflammation and intestinal and central nervous system barrier functions.

Abstract

Background: Toxoplasmosis promotes acute and chronic symptoms ranging from ocular to severe congenital or neurotoxoplasmosis. A proper host immune response and a healthy gut microbiota control the pathophysiology of toxoplasmosis, presenting an opportunity for pro-resolving mediators.

Objective: Here, we evaluated the role of the anti-inflammatory/pro-resolving protein annexin (Anx)A1 in Toxoplasma gondii (Tg) infection.

Results: AnxA1 levels increase in the brain during Tg infection, and AnxA1 knockout (KO) mice display higher susceptibility to disease, an increased number of brain cysts, an inflammatory response, severe lesions, and brain permeability, along with lower claudin-5 and occludin expression. Notably, AnxA1 deficiency increased the number of IBA-1⁺ cells in the brain, macrophages/neutrophils/dendritic cells producing IL-10 and TNF, and Th2 and CD8 T cells producing IL-17 compared to wild-type cells. An increased number of Tregs and innate cells producing TNF has been observed in the spleen. Moreover, the absence of AnxA1 increases gut inflammation, alters microbiota composition, reduces mucus production, increases intestinal permeability, and promotes bacterial translocation from the gut to the liver. Furthermore, imipenem treatment restored animal survival, prevented bacterial translocation into the liver, and reduced brain inflammation. = CONCLUSION: Collectively, our data demonstrate that AnxA1 is critical for regulating the pathogenesis of Tg infection and unveils a possible therapeutic target for this disease.