Pattern-recognition receptors (PRRs) including Toll-like receptors, RIG-I-like receptors, and cytoplasmic DNA receptors are essential for protection against pathogens but require tight control to avert inflammatory diseases. The mechanisms underlying this strict regulation are unclear. MYSM1 was previously described as a key component of epigenetic signaling machinery. We found that in response to microbial stimuli, MYSM1 accumulated in the cytoplasm where it interacted with and inactivated TRAF3 and TRAF6 complexes to terminate PRR pathways for pro-inflammatory and type I interferon responses. Consequently, Mysm1 deficiency in mice resulted in hyper-inflammation and enhanced viral clearance but also susceptibility to septic shock. We identified two motifs in MYSM1 that were essential for innate immune suppression: the SWIRM domain that interacted with TRAF3 and TRAF6 and the metalloproteinase domain that removed K63 polyubiquitins. This study identifies MYSM1 as a key negative regulator of the innate immune system that guards against an overzealous self-destructive immune response.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.immuni.2015.09.010 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The immune function of TLR4-1 gene in Octopus sinensis revealed by RNAi and RNA-seq.
Fish Shellfish Immunol
November 2024
State Key Laboratory of Mariculture Breeding, Fisheries College, Jimei University, Xiamen, 361021, China; Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture and Rural Affairs, Fisheries College, Jimei University, Xiamen, 361021, China. Electronic address:
Toll-like receptors (TLRs) are a class of conserved pattern recognition receptors (PRRs) that are crucial for initiating the innate immune response and aiding in the clearance of pathogenic organisms. Many studies have identified TLR4 as a distinctive member of the TLR family, capable of activating both the Myeloid differentiation factor 88-dependent signaling pathway (MyD88-dependent) and the TIR-domain-containing adaptor inducing IFN-β dependent signaling pathway (TRIF-dependent). Nevertheless, the role of TLR4 in Cephalopoda is still largely unexplored.
View Article and Find Full Text PDFGrouper OTUB1 and OTUB2 promote red-spotted grouper nervous necrosis virus (RGNNV) replication by inhibiting the host innate immune response.
Fish Shellfish Immunol
August 2024
College of Marine Sciences, South China Agricultural University, Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China; Nansha-South China Agricultural University Fishery Research Institute, Guangzhou, Guangzhou, 511400, China. Electronic address:
Red-spotted grouper nervous necrosis virus (RGNNV) is a major viral pathogen of grouper and is able to antagonize interferon responses through multiple strategies, particularly evading host immune responses by inhibiting interferon responses. Ovarian tumor (OTU) family proteins are an important class of DUBs and the underlying mechanisms used to inhibit interferon pathway activation are unknown. In the present study, primers were designed based on the transcriptome data, and the ovarian tumor (OTU) domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1) and OTUB2 genes of Epinephelus coioides (EcOTUB1 and EcOTUB2) were cloned and characterized.
View Article and Find Full Text PDFmiR-144 affects the immune response and activation of inflammatory responses in Cynoglossus semilaevis by regulating the expression of CsMAPK6.
Fish Shellfish Immunol
June 2024
College of Agriculture and Bioengineering, Heze University, Heze, 274000, China. Electronic address:
MicroRNAs are increasingly recognized for their pivotal role in the immune system, yet the specific regulatory functions of fish-derived microRNAs remain largely unexplored. In this research, we discovered a novel miRNA, Cse-miR-144, in the Chinese tongue sole (Cynoglossus semilaevis), characterized by a 73-base pair precursor and a 21-nucleotide mature sequence. Our findings revealed that the expression of Cse-miR-144 was notably inhibited by various Vibrio species.
View Article and Find Full Text PDFMST1/2 exerts a pivotal role in inducing neuroinflammation and Coxsackievirus-A10 replication by interacting with innate immunity.
Virol J
April 2024
Department of Respiratory Medicine, The First People's Hospital of Yunnan Province, Kunming, China.
Coxsackievirus-A10 (CV-A10), responsible for the hand, foot and mouth disease (HFMD) pandemic, could cause serious central nervous system (CNS) complications. The underlying molecular basis of CV-A10 and host interactions inducing neuropathogenesis is still unclear. The Hippo signaling pathway, historically known for a dominator of organ development and homeostasis, has recently been implicated as an immune regulator.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!