Humoral immunity prevents clinical malaria during Plasmodium relapses without eliminating gametocytes

Autoři: Chester J. Joyner aff001;  Cristiana F. A. Brito aff001;  Celia L. Saney aff001;  Regina Joice Cordy aff001;  Maren L. Smith aff001;  Stacey A. Lapp aff001;  Monica Cabrera-Mora aff001;  Shuya Kyu aff002;  Nicolas Lackman aff001;  Mustafa V. Nural aff001;  Jeremy D. DeBarry aff001aff001;  Jessica C. Kissinger aff001;  Mark P. Styczynski aff001;  F. Eun-Hyung Lee aff001;  Tracey J. Lamb aff001;  Mary R. Galinski aff001
Působiště autorů: Malaria Host–Pathogen Interaction Center, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States of America aff001;  Division of Pulmonary, Allergy, Critical Care, & Sleep Medicine, Department of Medicine, Emory University, Atlanta, GA, United States of America aff002;  Laboratory of Malaria, Centro de Pesquisas René Rachou–Fiocruz, Belo Horizonte, MG, Brazil aff003;  Department of Biology, Wake Forest University, Winston-Salem, North Carolina, United States of America aff004;  School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, United States of America aff005;  Institute of Bioinformatics, University of Georgia, Athens, GA, United States of America aff006;  Department of Genetics, University of Georgia, Athens, GA, United States of America aff007;  Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, United States of America aff008;  Lowance Center for Human Immunology, Emory University, Atlanta, GA, United States of America aff009;  Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, UT, United States of America aff010;  Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, United States of America aff011
Vyšlo v časopise: Humoral immunity prevents clinical malaria during Plasmodium relapses without eliminating gametocytes. PLoS Pathog 15(9): e32767. doi:10.1371/journal.ppat.1007974
Kategorie: Research Article


Plasmodium relapses are attributed to the activation of dormant liver-stage parasites and are responsible for a significant number of recurring malaria blood-stage infections. While characteristic of human infections caused by P. vivax and P. ovale, their relative contribution to malaria disease burden and transmission remains poorly understood. This is largely because it is difficult to identify ‘bona fide’ relapse infections due to ongoing transmission in most endemic areas. Here, we use the P. cynomolgi–rhesus macaque model of relapsing malaria to demonstrate that clinical immunity can form after a single sporozoite-initiated blood-stage infection and prevent illness during relapses and homologous reinfections. By integrating data from whole blood RNA-sequencing, flow cytometry, P. cynomolgi-specific ELISAs, and opsonic phagocytosis assays, we demonstrate that this immunity is associated with a rapid recall response by memory B cells that expand and produce anti-parasite IgG1 that can mediate parasite clearance of relapsing parasites. The reduction in parasitemia during relapses was mirrored by a reduction in the total number of circulating gametocytes, but importantly, the cumulative proportion of gametocytes increased during relapses. Overall, this study reveals that P. cynomolgi relapse infections can be clinically silent in macaques due to rapid memory B cell responses that help to clear asexual-stage parasites but still carry gametocytes.

Klíčová slova:

Medicine and health sciences – Parasitic diseases – Malaria – Immunology – Tropical diseases – Biology and life sciences – Cell biology – Cellular types – Animal cells – Immune cells – Antibody-producing cells – B cells – Blood cells – White blood cells – Germ cells – Gametocytes – Parasitology – Quantitative parasitology – Parasitemia – Parasite groups – Apicomplexa – Plasmodium – Organisms – Eukaryota – Protozoans – Parasitic protozoans – Malarial parasites – Animals – Vertebrates – Amniotes – Mammals – Primates – Monkeys – Old World monkeys – Macaque


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