NLRP10 Enhances CD4+ T-Cell-Mediated IFNγ Response via Regulation of Dendritic Cell-Derived IL-12 Release

• Main Authors: Vacca, Maurizio, Böhme, Julia, Zambetti, Lia Paola, 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, De Libero, Gennaro, Singhal, Amit, Mortellaro, Alessandra
• Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
• Format: Article
• Language: English
• Published: 2018
• Subjects: Mycobacterium Tuberculosis; Dendritic Cells
• Online Access: https://hdl.handle.net/10356/87419; http://hdl.handle.net/10220/44459
• Institution: Nanyang Technological University

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.