Qingming Xiong1, Xueqi Wang, Yasuko Rikihisa. 1. Department of Veterinary Biosciences, College of Veterinary Medicine, Ohio State University, Columbus, OH 43210, USA.
Abstract
BACKGROUND: Anaplasma phagocytophilum is an obligatory intracellular bacterium that infects granulocytes and causes human granulocytic anaplasmosis (HGA). This bacterium requires cholesterol for host cell infection in vitro and incorporates exogenous cholesterol into its membrane. METHODS: To understand the role of host cholesterol in A. phagocytophilum infection in vivo, we analyzed the effects of a high-cholesterol diet and reduced apolipoprotein E (apoE) activity on A. phagocytophilum infection in mice. RESULTS: A high-cholesterol diet significantly facilitated A. phagocytophilum infection in the spleen, liver, and blood of apoE-deficient (apoE(-/-)) mice, compared with the level of infection in apoE(-/-) mice fed a normal-cholesterol diet or wild-type (WT) mice fed a high- or normal-cholesterol diet. A. phagocytophilum infection induced a significant elevation in the mRNA expression of macrophage inflammatory protein (MIP)-2 and an MIP-2 receptor, CXCR2, in the spleen in apoE(-/-) mice fed a high-cholesterol diet, compared with the other 3 groups. CONCLUSION: Our results suggest that high blood cholesterol levels resulting from an interaction between dietary and genetic factors facilitate A. phagocytophilum infection and up-regulate a proinflammatory chemokine and its receptor, which may contribute to HGA pathogenesis.
BACKGROUND:Anaplasma phagocytophilum is an obligatory intracellular bacterium that infects granulocytes and causes humangranulocytic anaplasmosis (HGA). This bacterium requires cholesterol for host cell infection in vitro and incorporates exogenous cholesterol into its membrane. METHODS: To understand the role of host cholesterol in A. phagocytophiluminfection in vivo, we analyzed the effects of a high-cholesterol diet and reduced apolipoprotein E (apoE) activity on A. phagocytophiluminfection in mice. RESULTS: A high-cholesterol diet significantly facilitated A. phagocytophiluminfection in the spleen, liver, and blood of apoE-deficient (apoE(-/-)) mice, compared with the level of infection in apoE(-/-) mice fed a normal-cholesterol diet or wild-type (WT) mice fed a high- or normal-cholesterol diet. A. phagocytophiluminfection induced a significant elevation in the mRNA expression of macrophage inflammatory protein (MIP)-2 and an MIP-2 receptor, CXCR2, in the spleen in apoE(-/-) mice fed a high-cholesterol diet, compared with the other 3 groups. CONCLUSION: Our results suggest that high blood cholesterol levels resulting from an interaction between dietary and genetic factors facilitate A. phagocytophiluminfection and up-regulate a proinflammatory chemokine and its receptor, which may contribute to HGA pathogenesis.
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