Severe Malaria Infections Impair Germinal Center Responses by Inhibiting T Follicular Helper Cell Differentiation
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 infect...
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doaj-7d94e8cc18534b28b652d8d9af70eed82020-11-24T21:30:32ZengElsevierCell Reports2211-12472016-01-01141688110.1016/j.celrep.2015.12.006Severe Malaria Infections Impair Germinal Center Responses by Inhibiting T Follicular Helper Cell DifferentiationVictoria Ryg-Cornejo0Lisa Julia Ioannidis1Ann Ly2Chris Yu Chiu3Julie Tellier4Danika Lea Hill5Simon Peter Preston6Marc Pellegrini7Di Yu8Stephen Laurence Nutt9Axel Kallies10Diana Silvia Hansen11The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaMolecular Immunomodulation Laboratory, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Melbourne, VIC 3800, AustraliaThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, AustraliaNaturally 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-γ 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.http://www.sciencedirect.com/science/article/pii/S2211124715014187 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Severe Malaria Infections Impair Germinal Center Responses by Inhibiting T Follicular Helper Cell Differentiation Cell Reports |
author_facet |
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 |
author_sort |
Victoria Ryg-Cornejo |
title |
Severe Malaria Infections Impair Germinal Center Responses by Inhibiting T Follicular Helper Cell Differentiation |
title_short |
Severe Malaria Infections Impair Germinal Center Responses by Inhibiting T Follicular Helper Cell Differentiation |
title_full |
Severe Malaria Infections Impair Germinal Center Responses by Inhibiting T Follicular Helper Cell Differentiation |
title_fullStr |
Severe Malaria Infections Impair Germinal Center Responses by Inhibiting T Follicular Helper Cell Differentiation |
title_full_unstemmed |
Severe Malaria Infections Impair Germinal Center Responses by Inhibiting T Follicular Helper Cell Differentiation |
title_sort |
severe malaria infections impair germinal center responses by inhibiting t follicular helper cell differentiation |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2016-01-01 |
description |
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-γ 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. |
url |
http://www.sciencedirect.com/science/article/pii/S2211124715014187 |
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