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Complement receptor 1 is a sialic acid-independent erythrocyte receptor of Plasmodium falciparum
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نویسنده
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spadafora c. ,awandare g.a. ,kopydlowski k.m. ,czege j. ,moch j.k. ,finberg r.w. ,tsokos g.c. ,stoute j.a.
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منبع
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plos pathogens - 2010 - دوره : 6 - شماره : 6
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چکیده
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Plasmodium falciparum is a highly lethal malaria parasite of humans. a major portion of its life cycle is dedicated to invading and multiplying inside erythrocytes. the molecular mechanisms of erythrocyte invasion are incompletely understood. p. falciparum depends heavily on sialic acid present on glycophorins to invade erythrocytes. however,a significant proportion of laboratory and field isolates are also able to invade erythrocytes in a sialic acid-independent manner. the identity of the erythrocyte sialic acid-independent receptor has been a mystery for decades. we report here that the complement receptor 1 (cr1) is a sialic acid-independent receptor for the invasion of erythrocytes by p. falciparum. we show that soluble cr1 (scr1) as well as polyclonal and monoclonal antibodies against cr1 inhibit sialic acid-independent invasion in a variety of laboratory strains and wild isolates,and that merozoites interact directly with cr1 on the erythrocyte surface and with scr1- coated microspheres. also,the invasion of neuraminidase-treated erythrocytes correlates with the level of cr1 expression. finally,both sialic acid-independent and dependent strains invade cr1 transgenic mouse erythrocytes preferentially over wild-type erythrocytes but invasion by the latter is more sensitive to neuraminidase. these results suggest that both sialic acid-dependent and independent strains interact with cr1 in the normal red cell during the invasion process. however,only sialic acid-independent strains can do so without the presence of glycophorin sialic acid. our results close a longstanding and important gap in the understanding of the mechanism of erythrocyte invasion by p. falciparum that will eventually make possible the development of an effective blood stage vaccine.
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آدرس
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department of medicine,the uniformed services university of the health sciences,bethesda,md,united states,department of cellular injury,division of military casualty research,the walter reed army institute of research,silver spring,md,united states,instituto de investigaciones cientificas y servicios de alta tecnologia-aip,ciudad del saber,clayton, Panama, division of malaria vaccine development,the walter reed army institute of research,silver spring,md, United States, department of parasitology,division of experimental therapeutics,the walter reed army institute of research,silver spring,md,united states,us army medical materiel development activity (usammda),fort detrick,md, United States, biomedical instrumentation center,the uniformed services university of the health sciences,bethesda,md, United States, department of parasitology,division of experimental therapeutics,the walter reed army institute of research,silver spring,md, United States, department of medicine,university of massachusetts medical school,worcester,ma, United States, department of medicine,the uniformed services university of the health sciences,bethesda,md,united states,department of cellular injury,division of military casualty research,the walter reed army institute of research,silver spring,md,united states,department of medicine,beth israel deaconess medical center,harvard medical school,boston,ma, United States, department of medicine,the uniformed services university of the health sciences,bethesda,md,united states,department of cellular injury,division of military casualty research,the walter reed army institute of research,silver spring,md,united states,department of medicine,division of infectious diseases and epidemiology,pennsylvania state university college of medicine,hershey,pa, United States
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Authors
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