Fernandez-Arias Cristina, Rivera-Correa Juan, Gallego-Delgado Julio, Rudlaff Rachel, Fernandez Clemente, Roussel Camille, Götz Anton, Gonzalez Sandra, Mohanty Akshaya, Mohanty Sanjib, Wassmer Samuel, Buffet Pierre, Ndour Papa Alioune, Rodriguez Ana
Division of Parasitology, Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
Universidad Carlos III, 28911 Madrid, Spain.
Cell Host Microbe. 2016 Feb 10;19(2):194-203. doi: 10.1016/j.chom.2016.01.009.
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.
疟原虫是疟疾的致病寄生虫，它侵入红细胞进行繁殖，导致红细胞损失。然而，更大的损失是由未感染红细胞的清除引起的，有时在感染清除很久之后仍会发生。利用小鼠模型，我们发现疟原虫感染会诱导产生抗自身抗体，这些抗体与来自受感染但非未受感染小鼠的未感染红细胞表面结合。这些抗体识别磷脂酰丝氨酸，在疟疾期间，磷脂酰丝氨酸会暴露于一部分未感染红细胞的表面。我们发现，暴露磷脂酰丝氨酸的红细胞是表达高水平CD47（一种“别吃我”信号）的网织红细胞，但抗磷脂酰丝氨酸抗体的结合介导了它们的吞噬作用，从而导致贫血。在疟疾后晚期贫血的人类患者中，我们发现抗磷脂酰丝氨酸抗体水平与血浆血红蛋白之间存在强烈的负相关，这表明在人类中也有类似作用。抑制这一途径可能有助于治疗疟疾性贫血。
