High-cholesterol diet facilitates Anaplasma phagocytophilum infection and up-regulates macrophage inflammatory protein-2 and CXCR2 expression in apolipoprotein E-deficient mice.
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.


CONCLUSIONS
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.
Xiong
Qingming
Q
Department of Veterinary Biosciences, College of Veterinary Medicine, Ohio State University, Columbus, OH 43210, USA.
Wang
Xueqi
X
Rikihisa
Yasuko
Y
D041081:Anaplasma phagocytophilum; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D054426:Chemokine CXCL2; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D004195:Disease Models, Animal; D016873:Ehrlichiosis / Q000503:physiopathology*; D051379:Mice; D015846:Monokines / Q000235:genetics*; D023063:Receptors, Interleukin-8B / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001057:Apolipoproteins E; D054426:Chemokine CXCL2; D002791:Cholesterol, Dietary; D015846:Monokines; D023063:Receptors, Interleukin-8B; D002784:Cholesterol