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Extrafollicular CD4 T cell-derived IL-10 functions rapidly and transiently to support anti-Plasmodium humoral immunity
Journal article   Open access   Peer reviewed

Extrafollicular CD4 T cell-derived IL-10 functions rapidly and transiently to support anti-Plasmodium humoral immunity

Fionna A Surette, Jenna J Guthmiller, Lei Li, Alexandria J Sturtz, Rahul Vijay, Rosemary L Pope, Brandon L McClellan, Angela D Pack, Ryan A Zander, Peng Shao, …
PLoS pathogens, Vol.17(2), pp.e1009288-e1009288
02/01/2021
DOI: 10.1371/journal.ppat.1009288
PMCID: PMC7880450
PMID: 33529242
url
https://doi.org/10.1371/journal.ppat.1009288View
Published (Version of record) Open Access

Abstract

Immunity against malaria depends on germinal center (GC)-derived antibody responses that are orchestrated by T follicular helper (TFH) cells. Emerging data show that the regulatory cytokine IL-10 plays an essential role in promoting GC B cell responses during both experimental malaria and virus infections. Here we investigated the cellular source and temporal role of IL-10, and whether IL-10 additionally signals to CD4 T-cells to support anti-Plasmodium humoral immunity. Distinct from reports of virus infection, we found that IL-10 expressed by conventional, Foxp3-negative effector CD4 T cells and functioned in a B cell-intrinsic manner only during the first 96 hours of Plasmodium infection to support humoral immunity. The critical functions of IL-10 manifested only before the orchestration of GC responses and were primarily localized outside of B cell follicles. Mechanistically, our studies showed that the rapid and transient provision of IL-10 promoted B cell expression of anti-apoptotic factors, MHC class II, CD83, and cell-cell adhesion proteins that are essential for B cell survival and interaction with CD4 T cells. Together, our data reveal temporal features and mechanisms by which IL-10 critically supports humoral immunity during blood-stage Plasmodium infection, information that may be useful for developing new strategies designed to lessen the burden of malaria. Author summary Malaria is associated with the expression of both inflammatory and anti-inflammatory cytokines that together regulate disease severity and the function of parasite-specific immune cells subsets. Emerging data show that the anti-inflammatory cytokine Interleukin (IL)-10 can function to sustain an already established humoral immune response during acute and chronic virus infections. Unexpectedly, our results show that IL-10 functions only within the first 72-96 hours of Plasmodium blood-stage infection to promote initial helper T cell and B cell interactions, as well as B cell differentiation and survival. Our studies of the temporal features, spatial relationships, critical cellular sources and mechanisms by which IL-10 promotes humoral immunity during malaria highlight the distinct mechanisms governing anti-malarial immunity. This new information may lead to the identification of novel pathways and approaches for eliciting durable protection against malaria.
 Microbiology Parasitology Virology Life Sciences & Biomedicine Science & Technology

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