Journal article
Extrafollicular CD4 T cell-derived IL-10 functions rapidly and transiently to support anti-Plasmodium humoral immunity
FA Surette, JJ Guthmiller, L Li, AJ Sturtz, R Vijay, RL Pope, BL McClellan, AD Pack, RA Zander, P Shao, LYL Lan, D Fernandez-Ruiz, WR Heath, PC Wilson, NS Butler
Plos Pathogens | Published : 2021
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 was expressed by conventional, Foxp3-negative effector CD4 T cells and functioned in a B cellintrinsic manner only during the first 96 hours of Plasmodium infecti..
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Grants
Awarded by National Institutes of Health
Funding Acknowledgements
This work was supported by grants from the National Institutes of Health/National Institute of Allergy and Infectious Diseases (R01AI125446 and R01AI127481 to N.S.B.; T32AI007485 supported F.A.S.; T32AI007511 supported A.D.P.; P01AI097092 and HHSN272201400005C to P.C.W.), the National Institutes of Health/National Heart, Lung, and Blood Institute (T32HL007605 supported J.J.G.), the National Science Foundation (DBI 1559927 to BLM), the National Center for Research Resources of the National Institutes of Health under Award Number S10OD016199, the Australian Research Council (CE140100011 to W.R.H.) and the National Health and Medical Research Council (NHMRC; 1113293 and 1154457 to W.R.H.; 1139486 to D.F-R.). This work also utilized the Zeiss LSM710 confocal Microscope in the University of Iowa Central Microscopy Research Facilities that was purchased with funding from the National Institutes of Health/National Center for Research Resources (grant no. S10RR025439) and instruments in the University of Iowa Flow Cytometry Laboratories that were purchased with funding from the National Institutes of Health/National Cancer Institute (grant no. P30CA086862) and the National Institutes of Health/National Center for Research Resources (grant no. S10OD016199). The funders had no role in the study design, data collection design, data collection and analysis, decision to publish, or preparation of the manuscript.