ICAM-1 is a key receptor mediating cytoadherence and pathology in the Plasmodium chabaudi malaria model

Malaria Journal

Research

Blandine Franke-Fayard¹  Jai Ramesar¹  Deirdre A. Cunningham²  William Jarra²  Irene Tumwine²  Jean Langhorne²  Jing-wen Lin²  Garikai Kushinga²  Thibaut Brugat² 

[1] Leiden Malaria Research Group, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands;The Francis Crick Institute, NW1 1AT, London, UK;

关键词: Plasmodium chabaudi;    Sequestration;    ICAM-1;    CD36;    Schizont membrane-associated cytoadherence protein;    SMAC;   

DOI  :  10.1186/s12936-017-1834-8

 received in 2017-01-27, accepted in 2017-04-25,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundParasite cytoadherence within the microvasculature of tissues and organs of infected individuals is implicated in the pathogenesis of several malaria syndromes. Multiple host receptors may mediate sequestration. The identity of the host receptor(s), or the parasite ligand(s) responsible for sequestration of Plasmodium species other than Plasmodium falciparum is largely unknown. The rodent malaria parasites may be useful to model interactions of parasite species, which lack the var genes with their respective hosts, as other multigene families are shared between the species. The role of the endothelial receptors ICAM-1 and CD36 in cytoadherence and in the development of pathology was investigated in a Plasmodium chabaudi infection in C57BL/6 mice lacking these receptors. The schizont membrane-associated cytoadherence (SMAC) protein of Plasmodium berghei has been shown to exhibit reduced CD36-associated cytoadherence in P. berghei ANKA-infected mice.MethodsParasite tissue sequestration and the development of acute stage pathology in P. chabaudi infections of mice lacking CD36 or ICAM-1, their respective wild type controls, and in infections with mutant P. chabaudi parasites lacking the smac gene were compared. Peripheral blood parasitaemia, red blood cell numbers and weight change were monitored throughout the courses of infection. Imaging of bioluminescent parasites in isolated tissues (spleen, lungs, liver, kidney and gut) was used to measure tissue parasite load.ResultsThis study shows that neither the lack of CD36 nor the deletion of the smac gene from P. chabaudi significantly impacted on acute-stage pathology or parasite sequestration. By contrast, in the absence of ICAM-1, infected animals experience less anaemia and weight loss, reduced parasite accumulation in both spleen and liver and higher peripheral blood parasitaemia during acute stage malaria. The reduction in parasite tissue sequestration in infections of ICAM-1 null mice is maintained after mosquito transmission.ConclusionsThese results indicate that ICAM-1-mediated cytoadherence is important in the P. chabaudi model of malaria and suggest that for rodent malarias, as for P. falciparum, there may be multiple host and parasite molecules involved in sequestration.

【 授权许可】

CC BY   
© The Author(s) 2017