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

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 IFN? 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-?B activation. Defective IL-12 production was also evident in vivo and affected IFN? 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 IFN? induction in T cells and contributes to promote the host defense against Mtb. © 2017 Vacca, Böhme, Zambetti, Khameneh, Paleja, Laudisi, Ho, Neo, Leong, Marzuki, Lee, Poidinger, Santambrogio, Tsenova, Zolezzi, De Libero, Singhal and Mortellaro.