Influence of low-density lipoprotein (LDL) receptor on lipid composition, inflammation and parasitism during Toxoplasma gondii infection.
Intracellular replication of Toxoplasma gondii requires cholesterol uptake by host cell low-density lipoprotein receptor (LDLr), a critical element in atherosclerosis. We evaluated host parasitism, inflammatory responses and development of atherosclerosis in LDLr knockout (LDLr(-/-)) and their controls C57BL/6 mice infected with T. gondii. Our results show that T. gondii cysts were reduced in LDLr(-/-) mice when compared to C57BL/6 mice. However, in presence of hypercholesterolemic diet, parasite growth in LDLr(-/-) mice was similar to that seen in infected C57BL/6 mice. In presence of a hypercholesterolemic diet, T. gondii infection leads to a 60% reduction of serum triacylglycerol, total and atherogenic lipoprotein cholesterol. When aortic valve lesion was analyzed, infected mice showed a reduction of atherosclerotic lesion area as well as CD36 expression. MCP-1, SRA-I, SRA-II, ICAM-1 and VCAM-1 mRNA expression was kept similar between infected and control groups. Thus, despite the intense inflammatory process, the drastic reduction in serum lipids seems to limit the development of atherosclerosis in LDLr(-/-) mice infected with T. gondii. In conclusion, our results indicate that T. gondii employs host LDLr to acquire cholesterol and favor its growth. However, in the presence of hypercholesterolemia, T. gondii parasites are able to acquire cholesterol-rich lipoproteins through an alternative host receptor, and overcome LDLr deficiency, favoring host parasitism and impairing lipid loading of foam cells.
Portugal
Luciane R
LR
Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil.
Fernandes
Luciana R
LR
Pietra Pedroso
Vinícius S
VS
Santiago
Helton C
HC
Gazzinelli
Ricardo T
RT
Alvarez-Leite
Jacqueline I
JI
D000818:Animals; D001012:Aorta, Abdominal / Q000276:immunology / Q000503:physiopathology; D001013:Aorta, Thoracic / Q000276:immunology / Q000503:physiopathology; D001021:Aortic Valve / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000209:etiology; D018955:CD36 Antigens / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D006790:Host-Parasite Interactions; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency / Q000502:physiology*; D014122:Toxoplasma / Q000502:physiology*; D014123:Toxoplasmosis / Q000150:complications / Q000378:metabolism / Q000469:parasitology* / Q000503:physiopathology; D014280:Triglycerides / Q000097:blood
D018955:CD36 Antigens; D011973:Receptors, LDL; D014280:Triglycerides; D002784:Cholesterol