AUTHOR=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 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 8 - 2017

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01462

DOI=10.3389/fimmu.2017.01462

ISSN=1664-3224

ABSTRACT=<p>NLRP10 is a nucleotide-binding oligomerization domain-like receptor that functions as an intracellular pattern recognition receptor for microbial products. Here, we generated a <italic>Nlrp10<sup>−/−</sup></italic> mouse to delineate the role of NLRP10 in the host immune response and found that <italic>Nlrp10<sup>−/−</sup></italic> dendritic cells (DCs) elicited sub-optimal IFNγ production by antigen-specific CD4<sup>+</sup> T cells compared to wild-type (WT) DCs. In response to T-cell encounter, CD40 ligation or Toll-like receptor 9 stimulation, <italic>Nlrp10<sup>−/−</sup></italic> DCs produced low levels of IL-12, due to a substantial decrease in NF-κB activation. Defective IL-12 production was also evident <italic>in vivo</italic> and affected IFNγ production by CD4<sup>+</sup> T cells. Upon <italic>Mycobacterium tuberculosis</italic> (<italic>Mtb</italic>) infection, <italic>Nlrp10<sup>−/−</sup></italic> 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 <italic>Mtb</italic>.</p>