Severe Malaria Infections Impair Germinal Center Responses by Inhibiting T Follicular Helper Cell Differentiation
Victoria Ryg-Cornejo, Lisa Julia Ioannidis, Ann Ly, Chris Yu Chiu, Julie Tellier, Danika Lea Hill, Simon Peter Preston, Marc Pellegrini, Di Yu, Stephen Laurence Nutt, Axel Kallies, Diana Silvia Hansen
CELL REPORTS | CELL PRESS | Published : 2016
Naturally acquired immunity to malaria develops only after years of repeated exposure to Plasmodium parasites. Despite the key role antibodies play in protection, the cellular processes underlying the slow acquisition of immunity remain unknown. Using mouse models, we show that severe malaria infection inhibits the establishment of germinal centers (GCs) in the spleen. We demonstrate that infection induces high frequencies of T follicular helper (Tfh) cell precursors but results in impaired Tfh cell differentiation. Despite high expression of Bcl-6 and IL-21, precursor Tfh cells induced during infection displayed low levels of PD-1 and CXCR5 and co-expressed Th1-associated molecules such as ..View full abstract
Awarded by Australian Government National Health and Medical Research Council IRIISS
We wish to thank David Tarlinton, Dimitra Zotos, and Lynn Corcoran for scientific advice. This work was supported by the Australian Government National Health and Medical Research Council IRIISS and Project Grants 637345, 1031212, and 1058665; the Sylvia and Charles Viertel Foundation (to A.K.); the Australian Research Council (to S.L.N.); and the Victorian State Government Operational Infrastructure.