Journal article
cGAS-mediated control of blood-stage malaria promotes Plasmodium-specific germinal center responses
JCI insight, Vol.3(2), e94142
01/25/2018
DOI: 10.1172/jci.insight.94142
PMCID: PMC5821207
PMID: 29367469
Abstract
Sensing of pathogens by host pattern recognition receptors is essential for activating the immune response during infection. We used a nonlethal murine model of malaria (
Plasmodium yoelii 17XNL
) to assess the contribution of the pattern recognition receptor cyclic GMP-AMP synthase (cGAS) to the development of humoral immunity. Despite previous reports suggesting a critical, intrinsic role for cGAS in early B cell responses, cGAS-deficient (
cGAS
–/–
) mice had no defect in the early expansion or differentiation of
Plasmodium
-specific B cells. As the infection proceeded, however,
cGAS
–/–
mice exhibited higher parasite burdens and aberrant germinal center and memory B cell formation when compared with littermate controls. Antimalarial drugs were used to further demonstrate that the disrupted humoral response was not B cell intrinsic but instead was a secondary effect of a loss of parasite control. These findings therefore demonstrate that cGAS-mediated innate-sensing contributes to parasite control but is not intrinsically required for the development of humoral immunity. Our findings highlight the need to consider the indirect effects of pathogen burden in investigations examining how the innate immune system affects the adaptive immune response.
Utilizing a murine malaria model, cGAS is shown to contribute to parasite control but is dispensable for activation of CD4
+
T cells and B cells.
Details
- Title: Subtitle
- cGAS-mediated control of blood-stage malaria promotes Plasmodium-specific germinal center responses
- Creators
- William O Hahn - Department of Immunology, University of Washington, Seattle, Washington, USANoah S Butler - Department of Immunology, University of Washington, Seattle, Washington, USAScott E Lindner - Department of Immunology, University of Washington, Seattle, Washington, USAHolly M Akilesh - Department of Immunology, University of Washington, Seattle, Washington, USAD. Noah Sather - Department of Immunology, University of Washington, Seattle, Washington, USAStefan H.I Kappe - Department of Immunology, University of Washington, Seattle, Washington, USAJessica A Hamerman - Department of Immunology, University of Washington, Seattle, Washington, USAMichael Gale - Department of Immunology, University of Washington, Seattle, Washington, USAW. Conrad Liles - Department of Immunology, University of Washington, Seattle, Washington, USAMarion Pepper - Department of Immunology, University of Washington, Seattle, Washington, USA
- Resource Type
- Journal article
- Publication Details
- JCI insight, Vol.3(2), e94142
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/jci.insight.94142
- PMID
- 29367469
- PMCID
- PMC5821207
- ISSN
- 2379-3708
- eISSN
- 2379-3708
- Grant note
- R01 AI04002 / NIAID T32 AI007044-39 / NIAID U19 AI083019 / NIAID R01 AI118803 / NIAID
- Language
- English
- Date published
- 01/25/2018
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984001229002771
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