MilliporeSigma
  • Home
  • Search Results
  • Disruption of IL-21 signaling affects T cell-B cell interactions and abrogates protective humoral immunity to malaria.

Disruption of IL-21 signaling affects T cell-B cell interactions and abrogates protective humoral immunity to malaria.

PLoS pathogens (2015-03-13)
Damián Pérez-Mazliah, Dorothy Hui Lin Ng, Ana Paula Freitas do Rosário, Sarah McLaughlin, Béatris Mastelic-Gavillet, Jan Sodenkamp, Garikai Kushinga, Jean Langhorne
ABSTRACT

Interleukin-21 signaling is important for germinal center B-cell responses, isotype switching and generation of memory B cells. However, a role for IL-21 in antibody-mediated protection against pathogens has not been demonstrated. Here we show that IL-21 is produced by T follicular helper cells and co-expressed with IFN-γ during an erythrocytic-stage malaria infection of Plasmodium chabaudi in mice. Mice deficient either in IL-21 or the IL-21 receptor fail to resolve the chronic phase of P. chabaudi infection and P. yoelii infection resulting in sustained high parasitemias, and are not immune to re-infection. This is associated with abrogated P. chabaudi-specific IgG responses, including memory B cells. Mixed bone marrow chimeric mice, with T cells carrying a targeted disruption of the Il21 gene, or B cells with a targeted disruption of the Il21r gene, demonstrate that IL-21 from T cells signaling through the IL-21 receptor on B cells is necessary to control chronic P. chabaudi infection. Our data uncover a mechanism by which CD4+ T cells and B cells control parasitemia during chronic erythrocytic-stage malaria through a single gene, Il21, and demonstrate the importance of this cytokine in the control of pathogens by humoral immune responses. These data are highly pertinent for designing malaria vaccines requiring long-lasting protective B-cell responses.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Phenylacetic acid, suitable for plant cell culture
Sigma-Aldrich
L-Glutamine, ReagentPlus®, ≥99% (HPLC)
Sigma-Aldrich
Trypan Blue solution, 0.4%, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Phenylacetic acid, 99%
Sigma-Aldrich
Phenylacetic acid, ≥99%, FCC, FG
SAFC
L-Glutamine
Sigma-Aldrich
Trypan Blue solution, 0.4%, for microscopy
Supelco
Pyrimethamine, VETRANAL®, analytical standard
Sigma-Aldrich
L-Glutamine, BioUltra, ≥99.5% (NT)
Sigma-Aldrich
L-Glutamine, meets USP testing specifications, suitable for cell culture, 99.0-101.0%, from non-animal source
Sigma-Aldrich
L-Glutamine, γ-irradiated, BioXtra, suitable for cell culture
Supelco
L-Glutamine, certified reference material, TraceCERT®
Supelco
L-Glutamine, Pharmaceutical Secondary Standard; Certified Reference Material
USP
Pyrimethamine, United States Pharmacopeia (USP) Reference Standard
Pyrimethamine, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
L-Glutamine
Supelco
Aphidicolin, analytical standard
Sigma-Aldrich
Brefeldin A, from Penicillium brefeldianum, Ready Made Solution, 10 mg/mL in DMSO
Sigma-Aldrich
Sodium chloride, BioPerformance Certified, ≥99% (titration), suitable for insect cell culture, suitable for plant cell culture
SAFC
Sodium chloride solution, 5 M
Sigma-Aldrich
Brefeldin A, ≥99% (HPLC and TLC), BioXtra, for molecular biology
Sigma-Aldrich
Brefeldin A, from Penicillium brefeldianum, ≥99% (HPLC and TLC)
Sigma-Aldrich
Phorbol 12-myristate 13-acetate, ≥99% (TLC), film or powder
Sigma-Aldrich
Trypan Blue, Dye content 60 %
Sigma-Aldrich
Sodium chloride, AnhydroBeads, −10 mesh, 99.999% trace metals basis
Sigma-Aldrich
Sodium chloride, AnhydroBeads, −10 mesh, 99.99% trace metals basis
Sigma-Aldrich
Sodium chloride-35Cl, 99 atom % 35Cl
Sigma-Aldrich
Diethyl azodicarboxylate solution, 40 wt. % in toluene
Sigma-Aldrich
Sodium chloride, random crystals, optical grade, 99.9% trace metals basis
Sigma-Aldrich
Sodium chloride, 99.999% trace metals basis