NLRP10 enhances CD4+ T-cell-mediated IFNγ response via regulation of dendritic cell-derived IL-12 release

Maurizio Vacca, Julia Böhme, Lia Paola Zambetti, Hanif Javanmard Khameneh, Bhairav S. Paleja, Federica Laudisi, Adrian W.S. Ho, Kurt Neo, Keith Weng Kit Leong, Mardiana Marzuki, Bernett Lee, Michael Poidinger, Laura Santambrogio, Liana Tsenova, Francesca Zolezzi, Gennaro de Libero, Amit Singhal, Alessandra Mortellaro

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

NLRP10 is a nucleotide-binding oligomerization domain-like receptor that functions as an intracellular pattern recognition receptor for microbial products. Here, we generated a Nlrp10-/- mouse to delineate the role of NLRP10 in the host immune response and found that Nlrp10-/- dendritic cells (DCs) elicited sub-optimal IFNγ production by antigen-specific CD4+ T cells compared to wild-type (WT) DCs. In response to T-cell encounter, CD40 ligation or Toll-like receptor 9 stimulation, Nlrp10-/- DCs produced low levels of IL-12, due to a substantial decrease in NF-κB activation. Defective IL-12 production was also evident in vivo and affected IFNγ production by CD4+ T cells. Upon Mycobacterium tuberculosis (Mtb) infection, Nlrp10-/- mice displayed diminished T helper 1-cell responses and increased bacterial growth compared to WT mice. These data indicate that NLRP10-mediated IL-12 production by DCs is critical for IFNγ induction in T cells and contributes to promote the host defense against Mtb.

Original languageEnglish (US)
Article number1462
JournalFrontiers in immunology
Volume8
Issue numberNOV
DOIs
StatePublished - Nov 2 2017

Keywords

  • CpG DNA
  • Dendritic cells
  • IFNγ
  • IL-12
  • Mycobacterium tuberculosis
  • NLRP10
  • T helper 1
  • Toll-like receptor 9

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Vacca, M., Böhme, J., Zambetti, L. P., Khameneh, H. J., Paleja, B. S., Laudisi, F., Ho, A. W. S., Neo, K., Leong, K. W. K., Marzuki, M., Lee, B., Poidinger, M., Santambrogio, L., Tsenova, L., Zolezzi, F., de Libero, G., Singhal, A., & Mortellaro, A. (2017). NLRP10 enhances CD4+ T-cell-mediated IFNγ response via regulation of dendritic cell-derived IL-12 release. Frontiers in immunology, 8(NOV), [1462]. https://doi.org/10.3389/fimmu.2017.01462