Glycerol-3-phosphate acyltransferase 1 is essential for the immune response to infection with coxsackievirus B3 in mice.
Livers and hearts from mice deficient in glycerol-3-phosphate acyltransferase 1 (GPAT1; Gpat1(-/-)) have a decreased content of glycerolipid intermediates and triacylglycerol, an altered composition of liver phospholipids, and elevated markers of oxidative stress. Compared with control C57BL/6 mice, infection of Gpat1(-/-) mice with coxsackievirus B3 (CVB3) resulted in higher mortality, an approximately 50% increase in heart pathology, a significant increase in liver viral titers, and a 100-fold increase in heart viral titers. Moreover, heart mRNA levels for proinflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)-6, and IL-1B were increased in the Gpat1(-/-) mice. Loss of Gpat1 also resulted in dysregulation of specific immune cells. Splenic dendritic cells from Gpat1(-/-) mice were fully capable of stimulating T cells from control mice; however, splenic T cells from Gpat1(-/-) mice were defective in their response to CVB3 antigen. Our data indicate that a lack of GPAT1 activity affects 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.
Karlsson
Erik A
EA
Department of Nutrition, University of North Carolina, Chapel Hill, NC 27599, USA.
Wang
Shuli
S
Shi
Qing
Q
Coleman
Rosalind A
RA
Beck
Melinda A
MA
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D003384:Coxsackievirus Infections / Q000201:enzymology* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000201:enzymology / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D013154:Spleen / Q000201:enzymology / Q000276:immunology
D000956:Antigens, Viral; D016207:Cytokines; D012333:RNA, Messenger; D005992:Glycerol-3-Phosphate O-Acyltransferase