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 antigenspecific 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.
Vacca, Maurizio; Böhme, Julia; Zambetti, Lisa; Khameneh, Hanif Javanmard; Paleja, Bhairav S.; Laudisi, Federica; Ho, Adrian W. S.; Neo, Kurt; Leong, Keith Weng Kit; Marzuki, Mardiana; Lee, Bernett; Poidinger, Michael; Santambrogio, Laura; Tsenova, Liana; Zolezzi, Francesca; Libero, Gennaro De; Singhal, Amit; and Mortellaro, Alessandra, "NLRP10 Enhances CD4+ T-Cell-Mediated IFNγ Response via Regulation of Dendritic Cell-Derived IL-12 Release" (2017). CUNY Academic Works.