NLRP10 enhances Shigella-induced pro-inflammatory responses.
Members of the NLR family evolved as intracellular sensors for bacterial and viral infection. However, our knowledge on the implication of most of the human NLR proteins in innate immune responses still remains fragmentary. Here we characterized the role of human NLRP10 in bacterial infection. Our data revealed that NLRP10 is a cytoplasmic localized protein that positively contributes to innate immune responses induced by the invasive bacterial pathogen Shigella flexneri. SiRNA-mediated knock-down studies showed that NLRP10 contributes to pro-inflammatory cytokine release triggered by Shigella in epithelial cells and primary dermal fibroblasts, by influencing p38 and NF-κB activation. This effect is dependent on the ATPase activity of NLRP10 and its PYD domain. Mechanistically, NLRP10 interacts with NOD1, a NLR that is pivotally involved in sensing of invasive microbes, and both proteins are recruited to the bacterial entry point at the plasma membrane. Moreover, NLRP10 physically interacts with downstream components of the NOD1 signalling pathway, such as RIP2, TAK1 and NEMO. Taken together, our data revealed a novel role of NLRP10 in innate immune responses towards bacterial infection and suggest that NLRP10 functions as a scaffold for the formation of the NOD1-Nodosome.
Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.
Katja
K
Lautz
Anna
A
Damm
Maureen
M
Menning
Julia
J
Wenger
Alexander C
AC
Adam
Paola
P
Zigrino
Elisabeth
E
Kremmer
Thomas A
TA
Kufer
D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000276:immunology; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D005347:Fibroblasts / Q000276:immunology / Q000382:microbiology; D055785:Gene Knockdown Techniques; D006801:Humans; D007113:Immunity, Innate; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000378:metabolism; D053474:Nod1 Signaling Adaptor Protein / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping; D012763:Shigella flexneri / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D016207:Cytokines; D016328:NF-kappa B; C494352:NLRP10 protein, human; C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein; D000251:Adenosine Triphosphatases