title: Depletion of Phagocytic Cells during Nonlethal Plasmodium yoelii Infection Causes Severe Malaria Characterized by Acute Renal Failure in Mice.
abstract: In the current study, we examined the effects of depletion of phagocytes on the progression of Plasmodium yoelii 17XNL infection in mice. Strikingly, the depletion of phagocytic cells, including macrophages, with clodronate in the acute phase of infection significantly reduced peripheral parasitemia but increased mortality. Moribund mice displayed severe pathological damage, including coagulative necrosis in liver and thrombi in the glomeruli, fibrin deposition, and tubular necrosis in kidney. The severity of infection was coincident with the increased sequestration of parasitized erythrocytes, the systematic upregulation of inflammation and coagulation, and the disruption of endothelial integrity in the liver and kidney. Aspirin was administered to the mice to minimize the risk of excessive activation of the coagulation response and fibrin deposition in the renal tissue. Interestingly, treatment with aspirin reduced the parasite burden and pathological lesions in the renal tissue and improved survival of phagocyte-depleted mice. Our data imply that the depletion of phagocytic cells, including macrophages, in the acute phase of infection increases the severity of malarial infection, typified by multiorgan failure and high mortality.
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan.
authors.forename: Mohamad Alaa
authors.initials: MA
authors.lastname: Terkawi
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Nishimura
authors.affiliation: Department of Basic Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Furuoka
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan nisikawa@obihiro.ac.jp.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Nishikawa
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000503:physiopathology*; D000818:Animals; D002452:Cell Count; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D006801:Humans; D008288:Malaria / Q000150:complications* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D010586:Phagocytes / Q000166:cytology*; D010967:Plasmodium yoelii / Q000502:physiology*