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 language | English (US) |
|---|---|
| Article number | 1462 |
| Journal | Frontiers in Immunology |
| Volume | 8 |
| Issue number | NOV |
| DOIs | |
| State | Published - Nov 2 2017 |
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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
Cite this
NLRP10 enhances CD4+ T-cell-mediated IFNγ response via regulation of dendritic cell-derived IL-12 release. / 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.
In: Frontiers in Immunology, Vol. 8, No. NOV, 1462, 02.11.2017.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - NLRP10 enhances CD4+ T-cell-mediated IFNγ response via regulation of dendritic cell-derived IL-12 release
AU - Vacca, Maurizio
AU - Böhme, Julia
AU - Zambetti, Lia Paola
AU - Khameneh, Hanif Javanmard
AU - Paleja, Bhairav S.
AU - Laudisi, Federica
AU - Ho, Adrian W.S.
AU - Neo, Kurt
AU - Leong, Keith Weng Kit
AU - Marzuki, Mardiana
AU - Lee, Bernett
AU - Poidinger, Michael
AU - Santambrogio, Laura
AU - Tsenova, Liana
AU - Zolezzi, Francesca
AU - de Libero, Gennaro
AU - Singhal, Amit
AU - Mortellaro, Alessandra
PY - 2017/11/2
Y1 - 2017/11/2
N2 - 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.
AB - 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.
KW - CpG DNA
KW - Dendritic cells
KW - IFNγ
KW - IL-12
KW - Mycobacterium tuberculosis
KW - NLRP10
KW - T helper 1
KW - Toll-like receptor 9
UR - http://www.scopus.com/inward/record.url?scp=85032736230&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85032736230&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2017.01462
DO - 10.3389/fimmu.2017.01462
M3 - Article
AN - SCOPUS:85032736230
VL - 8
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
IS - NOV
M1 - 1462
ER -