ArticlePLoS pathogens2016
IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 67 citations in OpenAlex.
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- Stage specific immune responses to schistosomes may explain conflicting results in malaria-schistosome coinfection studies.Infectious Disease Modelling · 2025Article
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- Dual nature of type I interferon responses and feedback regulations by SOCS1 dictate malaria mortality.Journal of advanced research · 2025Article
- The impact of Plasmodium-driven immunoregulatory networks on immunity to malaria.Nature reviews. Immunology · 2024Review
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- Role of circulating T follicular helper subsets following Ty21a immunization and oral challenge with wild typeFrontiers in immunology · 2024Article
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- The link between circulating follicular helper T cells and autoimmunity.Nature reviews. Immunology · 2022Review
- ICOS Expression Is Required for Maintenance but Not the Formation of Germinal Centers in the Spleen in Response to Plasmodium yoelii Infection.Infection and immunity · 2022Article
- B cell-intrinsic TBK1 is essential for germinal center formation during infection and vaccination in mice.The Journal of experimental medicine · 2022Article
- The role of different components of the immune system against Plasmodium falciparum malaria: Possible contribution towards malaria vaccine development.Molecular and biochemical parasitology · 2021Review
- The spleen: "epicenter" in malaria infection and immunity.Journal of leukocyte biology · 2021Review
- Extrafollicular CD4 T cell-derived IL-10 functions rapidly and transiently to support anti-Plasmodium humoral immunity.PLoS pathogens · 2021Article
- T-follicular helper cells in malaria infection and roles in antibody induction.Oxford open immunology · 2021Review
- B cell intrinsic expression of IFNλ receptor suppresses the acute humoral immune response to experimental blood-stage malaria.Virulence · 2020Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parasite-specific antibodies protect against blood-stage Plasmodium infection. However, in malaria-endemic regions, it takes many months for naturally-exposed individuals to develop robust humoral immunity. Explanations for this have focused on antigenic variation by Plasmodium, but have considered less whether host production of parasite-specific antibody is sub-optimal. In particular, it is unclear whether host immune factors might limit antibody responses. Here, we explored the effect of Type I Interferon signalling via IFNAR1 on CD4+ T-cell and B-cell responses in two non-lethal murine models of malaria, P. chabaudi chabaudi AS (PcAS) and P. yoelii 17XNL (Py17XNL) infection. Firstly, we demonstrated that CD4+ T-cells and ICOS-signalling were crucial for generating germinal centre (GC) B-cells, plasmablasts and parasite-specific antibodies, and likewise that T follicular helper (Tfh) cell responses relied on B cells. Next, we found that IFNAR1-signalling impeded the resolution of non-lethal blood-stage infection, which was associated with impaired production of parasite-specific IgM and several IgG sub-classes. Consistent with this, GC B-cell formation, Ig-class switching, plasmablast and Tfh differentiation were all impaired by IFNAR1-signalling. IFNAR1-signalling proceeded via conventional dendritic cells, and acted early by limiting activation, proliferation and ICOS expression by CD4+ T-cells, by restricting the localization of activated CD4+ T-cells adjacent to and within B-cell areas of the spleen, and by simultaneously suppressing Th1 and Tfh responses. Finally, IFNAR1-deficiency accelerated humoral immune responses and parasite control by boosting ICOS-signalling. Thus, we provide evidence of a host innate cytokine response that impedes the onset of humoral immunity during experimental malaria.
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