The role of Fas in pathological giardiasis
Diarrheal disease presents a debilitating burden on many people and economies around the world. Many of these cases are caused by the protozoan parasite Giardia sp., which colonizes the small intestine of a wide range of hosts and disrupts normal digestive and absorptive processes within the gut. Malnutrition caused by giardiasis is largely immune-dependent; the pathology commonly observed within the infected small intestine is likely triggered by activated CD8+ T cells. Understanding the dynamic immune response to Giardia infection is paramount for eventually identifying therapeutic targets and improving preventative measures. We report an influx of FasL+ cells into the duodenum following infection in C57BL/6 mice. Ex vivo restimulation of splenic and mesenteric lymph node (MLN) lymphocytes revealed an IFN- dominant cytokine response, which is conducive for the expansion of activated, FasL expressing CD8+ T cell. This observation prompted us to explore the role of Fas as a potential mediator of Giardia-induced intestinal injury. We observed defective parasite clearance in mice lacking functional Fas (Faslpr). Despite a high parasite burden, Faslpr mice did not exhibit the hallmark signs of a Giardia-injured small intestine, such as reduced disaccharidase activity. Increased ezrin phosphorylation was observed to correlate with reduced disaccharidase in infected C57BL/6 but not Faslpr mice. Faslpr mice exhibited similar levels of enterocyte apoptosis compared to C57BL/6 mice throughout infection. Activated CD8+ T cells within the spleens of infected Faslpr mice were detected, which was likely a consequence of their lympho-proliferative phenotype as this phenomenon was absent in C57BL/6 mice.
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