Abstract
Plasmodium parasites significantly modify infected red blood cells to ensure their survival. They achieve this by exporting hundreds of parasite proteins into the red blood cell. These modifications and their impact on disease progression have been extensively studied. However, less is known about how malaria infection affects the entire population of red blood cells within a host, including both infected and uninfected cells. There is some evidence suggesting that the parasite can influence cells beyond its immediate host cell, affecting uninfected bystander cells. In this study, we report the discovery of a unique population of red blood cells characterized by the absence of CD71 and the presence of CD98. This CD71− CD98+ population appears only in mice infected with malaria. Our findings show that this population emerges due to the rapid and widespread loss of CD71 from both infected and uninfected reticulocytes (young red blood cells). We conducted a thorough characterization of this new cell population, including their biophysical properties and surface protein expression. Notably, these CD71− CD98+ cells were more resistant to parasite invasion compared to early reticulocytes. Furthermore, assessments of their osmotic stability and deformability suggest that they retain the characteristics of healthy red blood cells. Given that most Plasmodium species preferentially invade reticulocytes, this substantial and systemic remodeling of reticulocytes likely has a profound impact on malaria disease progression and pathology.
Biosketch
Prof Laurent RENIA
Professor of Infectious Diseases
Director of the Respiratory and Infectious Diseases
Lee Kong Chian School of Medicine, Nanyang Technological University
Senior Fellow and Principal Investigator, A*STAR Infectious Diseases Labs – AID Labs
Laurent Renia is currently a professor of infectious diseases and the director of the respiratory and Infectious Diseases Program at the Lee Kong Chian School of Medicine, and in the School of Biological Sciences, Nanyang Technological University. He is also a senior fellow and principal investigator of the A*STAR ID Labs.
He has obtained my Ph.D. in 1991 from University Pierre et Marie Curie (now Sorbonne University) in Paris, France, and did my post-doctoral at New York University (1991-1992) under Victor Nussenzweig. He returned to Paris in 1993 where he obtained a permanent position as a research scientist at the French National Institute of Health (INSERM). Between 2001-and 2006, he became research director at INSERM, co-director, and director of the Department of Immunology at the Institut Cochin. he first joined A*STAR as a senior principal investigator in the Singapore Immunology Network (SIgN) in 2007. He became its Executive Director in 2013 from 2020. In 2020, he founded the A*STAR ID Labs (A*STAR) as its Executive director. he holds an adjunct position at the French National Institute of Health (INSERM). His scientific interests cover the immunology of infectious disease, focusing on mosquito-borne and zoonotic diseases, and newly emerging viruses such as SARS-CoV-2. His research focuses on shaping new concepts based on the understanding of molecular and cellular mechanism immunity through the development of animal models and new assays and approaches. He has published more than 400 articles and book chapters.
Professor of Infectious Diseases
Director of the Respiratory and Infectious Diseases
Lee Kong Chian School of Medicine, Nanyang Technological University
Senior Fellow and Principal Investigator, A*STAR Infectious Diseases Labs – AID Labs
Laurent Renia is currently a professor of infectious diseases and the director of the respiratory and Infectious Diseases Program at the Lee Kong Chian School of Medicine, and in the School of Biological Sciences, Nanyang Technological University. He is also a senior fellow and principal investigator of the A*STAR ID Labs.
He has obtained my Ph.D. in 1991 from University Pierre et Marie Curie (now Sorbonne University) in Paris, France, and did my post-doctoral at New York University (1991-1992) under Victor Nussenzweig. He returned to Paris in 1993 where he obtained a permanent position as a research scientist at the French National Institute of Health (INSERM). Between 2001-and 2006, he became research director at INSERM, co-director, and director of the Department of Immunology at the Institut Cochin. he first joined A*STAR as a senior principal investigator in the Singapore Immunology Network (SIgN) in 2007. He became its Executive Director in 2013 from 2020. In 2020, he founded the A*STAR ID Labs (A*STAR) as its Executive director. he holds an adjunct position at the French National Institute of Health (INSERM). His scientific interests cover the immunology of infectious disease, focusing on mosquito-borne and zoonotic diseases, and newly emerging viruses such as SARS-CoV-2. His research focuses on shaping new concepts based on the understanding of molecular and cellular mechanism immunity through the development of animal models and new assays and approaches. He has published more than 400 articles and book chapters.