NLRC3 negatively regulates Pasteurella multocida-induced NF-κB signaling in rabbits. 2024

Mengjiao Guo, and Jiaqi Zhang, and Mingtao Li, and Xiaorong Zhang, and Yantao Wu
Jiangsu Co-Innovation Center for Prevention of Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, China.

Pasteurella multocida (P. multocida) is a significant zoonotic pathogen that has the ability to infect various animals. The inflammatory response caused by P. multocida and the negative regulatory mechanism are not completely understood. NOD-like receptor family CARD-containing 3 (NLRC3), an intracellular member of the NLR family, has been reported as a negative regulator in human. In this study, we aimed to explore the role of rabbit NLRC3 (rNLRC3) in P. multocida infection. Our findings revealed a negative correlation between the expression of rNLRC3 and inflammatory cytokines during P. multocida infection. The expression of rNLRC3 was reduced at the initial stage of P. multocida infection and then recovered. Furthermore, rNLRC3 significantly inhibited the activation of NF-κB by reducing phosphorylation and nuclear import of p65 in response to P. multocida infection. Additionally, overexpression of rNLRC3 attenuated the expression of pro-inflammatory cytokines IL-1β, IL-6, IL-8, and TNF-α. Moreover, we demonstrated that rNLRC3 diminished NF-κB activation by interacting with rTRAF4 and rTRAF6. Overexpression of rNLRC3 promoted P. multocida proliferation, while P. multocida proliferation decreased after knockdown of rNLRC3. We also found that the NACHT-LRR domain is a functional domain of rNLRC3 that regulates the NF-κB pathway. Our study suggests that rNLRC3 negatively regulates P. multocida-induced NF-κB signaling in rabbits. It can serve as a checkpoint to prevent dysfunctional inflammation.

UI MeSH Term Description Entries
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000070576 NLR Proteins Intracellular signaling proteins that are defined by the presence of a NUCLEOTIDE-binding region and LEUCINE-rich repeats. Their general structure consists of any of a variety of effector domains at their N-termini such as a caspase recruitment domain (CARD), a central nucleotide-binding domain, and a variable number of C-terminal leucine-rich repeats. They are important for pathogen recognition in the INNATE IMMUNE RESPONSE of animals and plants. Members of the NLR protein family include the NOD SIGNALING ADAPTOR PROTEINS. NOD-like Receptor,Nucleotide-Binding Domain Leucine-Rich Repeat Protein,NLR Protein,NOD-like Receptors,Nucleotide-binding Domain Leucine-rich Repeat Proteins,NOD like Receptor,NOD like Receptors,Nucleotide Binding Domain Leucine Rich Repeat Protein,Nucleotide binding Domain Leucine rich Repeat Proteins,Protein, NLR,Proteins, NLR,Receptor, NOD-like,Receptors, NOD-like
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D016207 Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Cytokine
D016328 NF-kappa B Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA. Immunoglobulin Enhancer-Binding Protein,NF-kappa B Complex,Nuclear Factor kappa B,Transcription Factor NF-kB,kappa B Enhancer Binding Protein,Ig-EBP-1,NF-kB,NF-kappaB,Nuclear Factor-Kappab,Complex, NF-kappa B,Enhancer-Binding Protein, Immunoglobulin,Factor NF-kB, Transcription,Factor-Kappab, Nuclear,Ig EBP 1,Immunoglobulin Enhancer Binding Protein,NF kB,NF kappa B Complex,NF kappaB,NF-kB, Transcription Factor,Nuclear Factor Kappab,Transcription Factor NF kB
D016979 Pasteurella multocida A species of gram-negative, facultatively anaerobic, rod-shaped bacteria normally found in the flora of the mouth and respiratory tract of animals and birds. It causes shipping fever (see PASTEURELLOSIS, PNEUMONIC); HEMORRHAGIC BACTEREMIA; and intestinal disease in animals. In humans, disease usually arises from a wound infection following a bite or scratch from domesticated animals.
D036341 Intercellular Signaling Peptides and Proteins Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal. Growth Factor,Growth Factors,Paracrine Peptide Factors,Paracrine Protein Factors,Factor, Growth,Factors, Growth,Peptide Factors, Paracrine

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