Plasmodium Cysteine Repeat Modular Proteins 3 and 4 are essential for malaria parasite transmission from the mosquito to the host

Malaria Journal

Research

Jai Ramesar¹  Chris J Janse¹  Kevin D Augustijn²  Andrew P Waters³  Sally G Moore⁴  Joanne Thompson⁴  Maria M Mota⁵  Bruno Douradinha⁶ 

[1] Department of Parasitology, Leiden University Medical Centre, 9600 RC, Postbus, Netherlands;Department of Parasitology, Leiden University Medical Centre, 9600 RC, Postbus, Netherlands;VU University Amsterdam, De Boelelaan 1081, 1081 HV, Amsterdam, Netherlands;Glasgow Biomedical Research Centre, University of Glasgow, G12 8QQ, Glasgow, UK;Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, EH9 3JT, Edinburgh, UK;Malaria Unit, Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisbon, Portugal;Malaria Unit, Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisbon, Portugal;Molecular Vaccinology Lab, Queensland Institute for Medical Research, 300 Herston Rd, Herston, Australia;

关键词: Salivary Gland;    Plasmodium;    Blood Stage;    Plasmodium Berghei;    Plasmodium Knowlesi;   

DOI  :  10.1186/1475-2875-10-71

 received in 2010-12-16, accepted in 2011-03-31,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundThe Plasmodium Cysteine Repeat Modular Proteins (PCRMP) are a family of four conserved proteins of malaria parasites, that contain a number of motifs implicated in host-parasite interactions. Analysis of mutants of the rodent parasite Plasmodium berghei lacking expression of PCRMP1 or 2 showed that these proteins are essential for targeting of P. berghei sporozoites to the mosquito salivary gland and, hence, for transmission from the mosquito to the mouse.MethodsIn this work, the role of the remaining PCRMP family members, PCRMP3 and 4, has been investigated throughout the Plasmodium life cycle by generation and analysis of P. berghei gene deletion mutants, Δpcrmp 3 and Δpcrmp 4. The role of PCRMP members during the transmission and hepatic stages of the Plasmodium lifecycle has been evaluated by light- and electron microscopy and by analysis of liver stage development in HEPG2 cells in vitro and by infecting mice with mutant sporozoites. In addition, mice were immunized with live Δpcrmp 3 and Δpcrmp 4 sporozoites to evaluate their immunization potential as a genetically-attenuated parasite-based vaccine.ResultsDisruption of pcrmp3 and pcrmp4 in P. berghei revealed that they are also essential for transmission of the parasite through the mosquito vector, although acting in a distinct way to pbcrmp1 and 2. Mutants lacking expression of PCRMP3 or PCRMP4 show normal blood stage development and oocyst formation in the mosquito and develop into morphologically normal sporozoites, but these have a defect in egress from oocysts and do not enter the salivary glands. Sporozoites extracted from oocysts perform gliding motility and invade and infect hepatocytes but do not undergo further development and proliferation. Furthermore, the study shows that immunization with Δcrmp3 and Δcrmp4 sporozoites does not confer protective immunity upon subsequent challenge.ConclusionsPCRMP3 and 4 play multiple roles during the Plasmodium life cycle; they are essential for the establishment of sporozoite infection in the mosquito salivary gland, and subsequently for development in hepatocytes. However, although Δpcrmp3 and Δpcrmp4 parasites are completely growth-impaired in the liver, immunization with live sporozoites does not induce the protective immune responses that have been shown for other genetically-attenuated parasites.

【 授权许可】

Unknown   
© Douradinha et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.