| First Author | Allen IC | Year | 2011 |
| Journal | Immunity | Volume | 34 |
| Issue | 6 | Pages | 854-65 |
| PubMed ID | 21703540 | Mgi Jnum | J:173995 |
| Mgi Id | MGI:5050761 | Doi | 10.1016/j.immuni.2011.03.026 |
| Citation | Allen IC, et al. (2011) NLRX1 Protein Attenuates Inflammatory Responses to Infection by Interfering with the RIG-I-MAVS and TRAF6-NF-kappaB Signaling Pathways. Immunity 34(6):854-65 |
| abstractText | The nucleotide-binding domain and leucine-rich-repeat-containing (NLR) proteins regulate innate immunity. Although the positive regulatory impact of NLRs is clear, their inhibitory roles are not well defined. We showed that Nlrx1(-/-) mice exhibited increased expression of antiviral signaling molecules IFN-beta, STAT2, OAS1, and IL-6 after influenza virus infection. Consistent with increased inflammation, Nlrx1(-/-) mice exhibited marked morbidity and histopathology. Infection of these mice with an influenza strain that carries a mutated NS-1 protein, which normally prevents IFN induction by interaction with RNA and the intracellular RNA sensor RIG-I, further exacerbated IL-6 and type I IFN signaling. NLRX1 also weakened cytokine responses to the 2009 H1N1 pandemic influenza virus in human cells. Mechanistically, Nlrx1 deletion led to constitutive interaction of MAVS and RIG-I. Additionally, an inhibitory function is identified for NLRX1 during LPS activation of macrophages where the MAVS-RIG-I pathway was not involved. NLRX1 interacts with TRAF6 and inhibits NF-kappaB activation. Thus, NLRX1 functions as a checkpoint of overzealous inflammation. |
