Humoral immunity prevents clinical malaria during Plasmodium relapses without eliminating gametocytes

• Type of Material: Article
• Authors: Chester J. Joyner, Emory University; Cristiana F. A. Brito, Emory University; Celia L. Saney, Emory University; Regina Joice Cordy, Emory University; Maren L. Smith, Emory University; Stacey A. Lapp, Emory University; Monica Cabrera-Mora, Emory University; Shuya Kyu, Emory University; Nicolas Lackman, Emory University; Mustafa V. Nural, Emory University; Jeremy D. DeBarry, Emory University; Jessica C. Kissinger, Emory University; F. Eun-Hyung Lee, Emory University; Mark P. Styczynski, Emory University; Tracey J. Lamb, Emory University; Mary Galinski, Emory University
• Language: English
• Date: 2019-09-01
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: Copyright © 2019 Joyner et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.ppat.1007974
• Title of Journal or Parent Work: PLoS Pathogens
• ISSN: 1553-7366
• Volume: 15
• Issue: 9
• Start Page: e1007974
• End Page: e1007974
• Grant/Funding Information: This project was funded in part by Federal funds from the US National Institute of Allergy and Infectious Diseases (https://www.niaid.nih.gov), National Institutes of Health, Department of Health and Human Services under contract # HHSN272201200031C (PI: Mary R. Galinski), which established the Malaria Host-Pathogen Interaction Center (MaHPIC), as well as the Office of Research Infrastructure Programs/OD P51OD011132. The Yerkes NHP Genomics Core is supported in part by ORIP/OD P51OD011132.; Additional support was provided by 1R01AI121252, 1P01AI125180, P01A1078907, U19AI109962, and 1R01AI123425.
• Keywords: MEMORY B-CELLS; Parasitology; COMPLEXITY; GENETIC DIVERSITY; VIVAX; ANEMIA; INFECTIONS; Microbiology; PARASITE; FALCIPARUM; VACCINE; Virology; Life Sciences & Biomedicine; CYNOMOLGI; Science & Technology
• Research Categories: Health Sciences, Immunology; Biology, Parasitology; Health Sciences, Medicine and Surgery

Abstract

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.