Autoimmunity to phosphatidylserine and anemia in African Trypanosome infections

by Juan Rivera-Correa, Joseph Verdi, Julian Sherman, Jeremy M. Sternberg, Jayne Raper, Ana Rodriguez Anemia caused by trypanosome infection is poorly understood. Autoimmunity duringTrypanosoma brucei infection was proposed to have a role during anemia, but the mechanisms involved during this pathology have not been elucidated. In mouse models and human patients infected with malaria parasites, atypical B-cells promote anemia through the secretion of autoimmune anti-phosphatidylserine (anti-PS) antibodies that bind to uninfected erythrocytes and facilitate their clearance. Using mouse models of two trypanosome infections,Trypanosoma brucei andTrypanosoma cruzi, we assessed levels of autoantibodies and anemia. Our results indicate that acuteT.brucei infection, but notT.cruzi, leads to early increased levels of plasma autoantibodies against different auto antigens tested (PS, DNA and erythrocyte lysate) and expansion of atypical B cells (ABCs) that secrete these autoantibodies.In vitro studies confirmed that a lysate ofT.brucei, but notT.cruzi, could directly promote the expansion of these ABCs. PS exposure on erythrocyte plasma membrane seems to be an important contributor to anemia by delaying erythrocyte recovery since treatment with an agent that prevents binding to it (Annexin V) ameliorated anemia inT.brucei-infected mice. Analysis of the plasma of patients with human African trypanosomiasis (HAT) revealed high levels of anti-PS antibodies that correlated with anemia. Alt...
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research