Immune response to viral infection in mice lacking glycerol‐3‐phosphate acyltransferase 1 (GPAT1) is dysfunctional

Abstract

Mice deficient in GPAT1 (Gpat1−/−) have decreased content of lipid intermediates in the pathway of liver triacylglycerol synthesis, altered composition of liver phospholipids and elevated markers of oxidative stress. Compared with wildtype mice, infecting Gpat1−/− mice with coxsackievirus B3 (CVB3) resulted in increased mortality and a significant increase in both heart pathology and heart viral titers. Moreover, heart mRNA levels for proinflammatory cytokines TNF‐α, IL‐6 and IL‐1β were increased in the Gpat1−/− mice. To further characterize the effect of a lack of GPAT activity on the immune response to CVB3 infection, we used flow cytometry to determine the phenotype of the inflammatory cells infiltrating the heart. We observed an increased number of double‐positive T cells in the hearts of Gpat1−/− compared to wildtype mice. In addition, splenic T cells from Gpat1−/− mice were defective in their response to CVB3 antigen. However, splenic dendritic cells from Gpat1−/− mice were fully capable of stimulating T cells from wildtype mice. Taken together, our data suggests that a lack of GPAT1 activity appears to affect both innate and adaptive immune mechanisms. Innate mechanisms may be affected by altered membrane composition or host redox status whereas the adaptive response may require GPAT1 activity itself.