Anti-Self Phosphatidylserine Antibodies Recognize Uninfected Erythrocytes Promoting Malarial Anemia

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Show simple item record Fernandez Arias, Cristina Rivera Correa, Juan Gallego Delgado, Julio Rudlaff, Rachel Fernández Arias, Clemente Roussel, Camille Göetz, Anton González, Sandra Mohanty, Akshaya Mohanty, Sanjib Wassmer, Samuel Buffet, Pierre Ndour, Papa Alioune Rodriguez, Ana 2020-07-15T11:48:04Z 2020-07-15T11:48:04Z 2016-02-10
dc.identifier.bibliographicCitation Cell Host & Microbe, 19(2), 2016, pp. 194-203
dc.identifier.issn 1931-3128
dc.description.abstract Plasmodium species, the parasitic agents of malaria, invade erythrocytes to reproduce, resulting in erythrocyte loss. However, a greater loss is caused by the elimination of uninfected erythrocytes, sometimes long after infection has been cleared. Using a mouse model, we found that Plasmodium infection induces the generation of anti-self antibodies that bind to the surface of uninfected erythrocytes from infected, but not uninfected, mice. These antibodies recognize phosphatidylserine, which is exposed on the surface of a fraction of uninfected erythrocytes during malaria. We find that phosphatidylserine-exposing erythrocytes are reticulocytes expressing high levels of CD47, a "do-not-eat-me'' signal, but the binding of anti-phosphatidylserine antibodies mediates their phagocytosis, contributing to anemia. In human patients with late postmalarial anemia, we found a strong inverse correlation between the levels of anti-phosphatidylserine antibodies and plasma hemoglobin, suggesting a similar role in humans. Inhibition of this pathway may be exploited for treating malarial anemia.
dc.description.sponsorship This work was supported in part by a postdoctoral fellowship from the Ministerio de Ciencia e Innovacion, Spain, to C.F.-A., by the National Institutes of Health (NIH) institutional training grant 5T32AI100853-03 to J.R.-C., by a Burroughs Wellcome Fund Award for Investigators in the Pathogenesis of Infectious Disease to A.R., by a Dana Foundation award for Neuroimmunology to A.R., by the Labex GR-EX to C.R. and to P.A.N., and by the NIH National Institute of Allergy and Infectious Diseases grant U19AI089676-01S1 to S.W. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Anti-MSP-1 antibody was obtained through BEI Resources, NIAID, NIH. We would like to thank the director of Ispat General Hospital in Rourkela, as well as the director of the Institute of Life Sciences in Bubhaneshwar for allowing us to use the institute’s facilities at Anusandhan Laboratory in Rourkela. We are thankful to Andre Ballesteros-Tato for helpful discussions.
dc.language.iso eng
dc.publisher Elsevier
dc.rights © 2016 Elsevier Inc. All rights reserved.
dc.subject.other Plasmodium Falciparum Malaria
dc.subject.other Red blood cells
dc.subject.other Antiphospholipid antibodies
dc.subject.other Delayed hemolysis
dc.subject.other Parasitized erythrocytes
dc.subject.other Autoantibodies
dc.subject.other Infections
dc.subject.other Artesunate
dc.subject.other Children
dc.subject.other Mice
dc.title Anti-Self Phosphatidylserine Antibodies Recognize Uninfected Erythrocytes Promoting Malarial Anemia
dc.type article
dc.subject.eciencia Matemáticas
dc.rights.accessRights closedAccess
dc.type.version publishedVersion
dc.identifier.publicationfirstpage 194
dc.identifier.publicationissue 2
dc.identifier.publicationlastpage 203
dc.identifier.publicationtitle Cell Host & Microbe
dc.identifier.publicationvolume 19
dc.identifier.uxxi AR/0000017726
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