Severe malaria infections impair germinal center responses by inhibiting T follicular helper cell differentiation
- Author(s)
- Ryg-Cornejo, V; Ioannidis, LJ; Ly, A; Chiu, CY; Tellier, J; Hill, DL; Preston, SP; Pellegrini, M; Yu, D; Nutt, SL; Kallies, A; Hansen, DS;
- Details
- Publication Year 2016-01-05,Volume 14,Issue #1,Page 68-81
- Journal Title
- Cell Rep
- Publication Type
- Journal Article
- Abstract
- 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 T-bet and CXCR3. Blockade of the inflammatory cytokines TNF and IFN-gamma or T-bet deletion restored Tfh cell differentiation and GC responses to infection. Thus, this study demonstrates that the same pro-inflammatory mediators that drive severe malaria pathology have detrimental effects on the induction of protective B cell responses.
- Publisher
- Cell Press
- Research Division(s)
- Molecular Immunology; Infection And Immunity
- PubMed ID
- 26725120
- Publisher's Version
- https://doi.org/10.1016/j.celrep.2015.12.006
- Open Access at Publisher's Site
http://www.sciencedirect.com/science/article/pii/S2211124715014187- NHMRC Grants
- NHMRC/637345, NHMRC/1031212, NHMRC/1058665,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2016-01-13 02:34:11
Last Modified: 2016-01-13 03:18:12