Details

Autor(en) / Beteiligte

• Joyner, Chester J
• Brito, Cristiana F A
• Saney, Celia L
• Joice Cordy, Regina
• Smith, Maren L
• Lapp, Stacey A
• Cabrera-Mora, Monica
• Kyu, Shuya
• Lackman, Nicolas
• Nural, Mustafa V
• DeBarry, Jeremy D
• Kissinger, Jessica C
• Styczynski, Mark P
• Lee, F Eun-Hyung
• Lamb, Tracey J
• Galinski, Mary R
• Stevenson, Mary M.

Titel

Humoral immunity prevents clinical malaria during Plasmodium relapses without eliminating gametocytes

Ist Teil von

• PLoS pathogens, 2019-09, Vol.15 (9), p.e1007974-e1007974

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2019

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.