Characterization of anti-erythrocyte and anti-platelet antibodies in hemolytic anemia and thrombocytopenia induced by Plasmodium spp. and Babesiaspp. infection in mice

Introduction Malaria and Babesiosis are acute zoonotic disease that caused by infection with the parasite in the phylum Apicomplexa. Severe anemia and thrombocytopenia are the most common hematological complication of malaria and babesiosis. However, the mechanisms involved have not been elucidated, and only a few researches focus on the possible role of anti-erythrocyte and anti-platelet antibodies. Methods In this study, the Plasmodium yoelii, P. chabaudi, Babesia microti and B. rodhaini infected SCID and ICR mice. The parasitemia, survival rate, platelet count, anti-platelet antibodies, and the level of IFN-γ and interleukin (IL) -10 was tested after infection. Furthermore, the P. yoelii, P. chabaudi, B. rodhaini and B. microti infected ICR mice were treated with artesunate and diminaze, the development of the anti-erythrocyte and anti-platelet antibodies in chronic stage were examined. At last, the murine red blood cell and platelet membrane proteins probed with auto-antibodies induced by P. yoelii, P. chabaudi, B. rodhaini, and B. microti infection were characterized by proteomic analysis. Results and discussion The high anti-platelet and anti-erythrocyte antibodies were detected in ICR mice after P. yoelii, P. chabaudi, B. rodhaini, and B. microti infection. Actin of murine erythrocyte and platelet is a common auto-antigen in Plasmodium and Babesia spp. infected mice. Our findings indicate that anti-erythrocyte and anti-platelet autoantibodies contribute to thrombocytopenia and anemia associated with Plasmodium spp. and Babesia spp. infection. This study will help to understand the mechanisms of malaria and babesiosis-related thrombocytopenia and hemolytic anemia.

[1]  S. Richards,et al.  Retrospective spatiotemporal analysis of malaria cases reported between 2000 and 2020 in North Carolina, USA. , 2022, Travel medicine and infectious disease.

[2]  I. Igarashi,et al.  Repurposing of the Malaria Box for Babesia microti in mice identifies novel active scaffolds against piroplasmosis , 2022, Parasites & Vectors.

[3]  P. Krause,et al.  Human Babesiosis. , 2022, Infectious disease clinics of North America.

[4]  Jingze Liu,et al.  The regulatory strategy of proteins in the mouse kidney during Babesia microti infection. , 2022, Experimental parasitology.

[5]  H. Alzan,et al.  The Structural Basis of Babesia orientalis Lactate Dehydrogenase , 2022, Frontiers in Cellular and Infection Microbiology.

[6]  I. Igarashi,et al.  Compounds from the Medicines for Malaria Venture Box Inhibit In Vitro Growth of Babesia divergens, a Blood-Borne Parasite of Veterinary and Zoonotic Importance , 2021, Molecules.

[7]  B. Pilmis,et al.  A typical babesiosis in an immunocompetent patient. , 2021, Annales de Biologie Clinique.

[8]  I. Zafar,et al.  In vitro screening of novel anti-Babesia gibsoni drugs from natural products. , 2021, Parasitology international.

[9]  A. Fenves,et al.  Severe babesiosis with associated splenic infarcts and asplenia , 2021, Proceedings.

[10]  Yali Sun,et al.  Erythrocyte Adhesion of Merozoite Surface Antigen 2c1 Expressed During Extracellular Stages of Babesia orientalis , 2021, Frontiers in Immunology.

[11]  D. Cuthbert,et al.  Babesiosis in the Emergency Department: A Case Report. , 2021, The Journal of emergency medicine.

[12]  K. Bakirhan,et al.  Autoimmune Hemolytic Anemia Associated With Human Babesiosis , 2021, Journal of hematology.

[13]  M. Bednarska,et al.  Impact of Babesia microti infection on the initiation and course of pregnancy in BALB/c mice , 2021, Parasites & vectors.

[14]  Björn F. C. Kafsack,et al.  Activity Comparison of Epigenetic Modulators against the Hemoprotozoan Parasites Babesia divergens and Plasmodium falciparum. , 2021, ACS infectious diseases.

[15]  G. Shanks,et al.  Historical Perspective: The Evolution of Post-exposure Prophylaxis for Vivax Malaria Since the Korean War. , 2021, MSMR.

[16]  R. Culleton,et al.  Purification of Plasmodium and Babesia- infected erythrocytes using a non-woven fabric filter. , 2020, Tropical biomedicine.

[17]  C. Du,et al.  [Clinical characteristics, diagnosis and treatment of human babesiosis: a review]. , 2020, Zhongguo xue xi chong bing fang zhi za zhi = Chinese journal of schistosomiasis control.

[18]  J. Mosqueda,et al.  Assay methods for in vitro and in vivo anti-Babesia drug efficacy testing: Current progress, outlook, and challenges. , 2019, Veterinary parasitology.

[19]  A. Adegnika,et al.  Description of Plasmodium falciparum infections in central Gabon demonstrating high parasite densities among symptomatic adolescents and adults , 2019, Malaria Journal.

[20]  L. Tierney,et al.  Babesiosis-Associated Warm Autoimmune Hemolytic Anemia , 2019, Journal of General Internal Medicine.

[21]  D. Hui,et al.  Emerging and Reemerging Infectious Diseases: Global Overview , 2019, Infectious Disease Clinics of North America.

[22]  Yali Sun,et al.  Identification of a novel thrombospondin-related anonymous protein (BoTRAP2) from Babesia orientalis , 2019, Parasites & Vectors.

[23]  Delong Liu,et al.  Autoimmune hemolytic anemia associated with babesiosis , 2017, Biomarker Research.

[24]  L. Jian,et al.  [Investigation of two blood parasitic protozoa infection in farmed Macaca fascicularis in Guangxi Zhuang Autonomous Region]. , 2016, Zhongguo xue xi chong bing fang zhi za zhi = Chinese journal of schistosomiasis control.

[25]  G. Schett,et al.  B cells are critical for autoimmune pathology in Scurfy mice , 2013, Proceedings of the National Academy of Sciences.

[26]  W. Monteiro,et al.  Thrombocytopenia in Plasmodium vivax Malaria Is Related to Platelets Phagocytosis , 2013, PloS one.

[27]  X. Xuan,et al.  Macrophages Are Critical for Cross-Protective Immunity Conferred by Babesia microti against Babesia rodhaini Infection in Mice , 2011, Infection and Immunity.

[28]  M. Lacerda,et al.  Thrombocytopenia in malaria: who cares? , 2011, Memorias do Instituto Oswaldo Cruz.

[29]  K. Tung,et al.  Regulatory T cells control tolerogenic versus autoimmune response to sperm in vasectomy , 2011, Proceedings of the National Academy of Sciences.

[30]  Sujoy K. Modak,et al.  Childhood Plasmodium vivax malaria with severe thrombocytopenia and bleeding manifestations. , 2009, Journal of pediatric hematology/oncology.

[31]  G. Smyth,et al.  Platelets Kill Intraerythrocytic Malarial Parasites and Mediate Survival to Infection , 2009, Science.

[32]  A. Rodríguez-Morales,et al.  Occurrence of thrombocytopenia in Plasmodium vivax malaria. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[33]  J. Piette,et al.  Platelet autoantibodies and lupus‐associated thrombocytopenia , 2002, British journal of haematology.

[34]  Jianzhu Chen,et al.  Accelerated development of IgG autoantibodies and autoimmune disease in the absence of secreted IgM. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[35]  A. Capron,et al.  T-cell-dependent immunity and thrombocytopenia in rats infected with Plasmodium chabaudi , 1992, Infection and immunity.

[36]  A. Borne,et al.  The serology and immunochemistry of HIV-induced platelet-bound immunoglobulin , 1989, Blut.

[37]  Yasutaka Ueda [Advances in understanding the pathogenesis and treatment of autoimmune hemolytic anemia]. , 2022, [Rinsho ketsueki] The Japanese journal of clinical hematology.