Slc15a4 function is required for intact class switch recombination to IgG2c in response to TLR9 stimulation

Pia Dosenovic, Monika Ádori, William C. Adams, Gabriel K. Pedersen, Martina Soldemo, Bruce Beutler, Gunilla B Karlsson Hedestam

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Signalling through Toll-like receptors (TLRs) by endogenous components of viruses or bacteria can promote antibody (Ab) isotype switching to IgG2a/c. Multiple cell types are capable of responding to TLR stimulation in vivo and the processes underlying TLR-induced Ab isotype switching are not fully defined. Here, we used feeble mice, which are deficient in the peptide/histidine transporter solute carrier family 15 member 4 (Slc15a4), and fail to produce cytokines including interferon alpha (IFNα) in response to TLR9 stimulation, to study Ab isotype switching to IgG2c in response to vaccination. We demonstrate that the production of IgG2c in response to CpGA-adjuvanted vaccines was severely reduced in feeble mice, while a more subtle defect was observed for CpGB. The reduced IgG2c production in feeble could not be ascribed to defective plasmacytoid dendritic cell (pDC) responses alone as we found that splenic cDCs and B cells from feeble mice were also defective in response to TLR9 ligation ex vivo. We conclude that Slc15a4 is required for intact function of TLR9-expressing cells and for effective Ab isotype switching to IgG2c in response to CpG-adjuvanted vaccines.

Original languageEnglish (US)
Pages (from-to)136-146
Number of pages11
JournalImmunology and Cell Biology
Volume93
Issue number2
DOIs
StatePublished - Feb 12 2015

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Immunoglobulin Class Switching
Genetic Recombination
Toll-Like Receptors
Antibodies
Vaccines
Viral Structures
Histidine
Interferon-alpha
Dendritic Cells
Ligation
Vaccination
B-Lymphocytes
Cytokines
Bacteria

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

Cite this

Slc15a4 function is required for intact class switch recombination to IgG2c in response to TLR9 stimulation. / Dosenovic, Pia; Ádori, Monika; Adams, William C.; Pedersen, Gabriel K.; Soldemo, Martina; Beutler, Bruce; Hedestam, Gunilla B Karlsson.

In: Immunology and Cell Biology, Vol. 93, No. 2, 12.02.2015, p. 136-146.

Research output: Contribution to journalArticle

Dosenovic, Pia ; Ádori, Monika ; Adams, William C. ; Pedersen, Gabriel K. ; Soldemo, Martina ; Beutler, Bruce ; Hedestam, Gunilla B Karlsson. / Slc15a4 function is required for intact class switch recombination to IgG2c in response to TLR9 stimulation. In: Immunology and Cell Biology. 2015 ; Vol. 93, No. 2. pp. 136-146.
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