scholarly journals PKA/KIN-1 mediates innate immune responses to bacterial pathogens in Caenorhabditis elegans

2017 ◽  
Vol 23 (8) ◽  
pp. 656-666 ◽  
Author(s):  
Yi Xiao ◽  
Fang Liu ◽  
Pei-ji Zhao ◽  
Cheng-Gang Zou ◽  
Ke-Qin Zhang
Keyword(s):  
Innate Immunity ◽  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Immune Responses ◽  
Innate Immune ◽  
Autophagic Flux ◽  
Innate Immune Responses ◽  
C Elegans ◽  
Downstream Effector ◽  
Model Animal

The genetically tractable organism Caenorhabditis elegans is a powerful model animal for the study of host innate immunity. Although the intestine and the epidermis of C. elegans that is in contact with pathogens are likely to function as sites for the immune function, recent studies indicate that the nervous system could control innate immunity in C. elegans. In this report, we demonstrated that protein kinase A (PKA)/KIN-1 in the neurons contributes to resistance against Salmonella enterica infection in C. elegans. Microarray analysis revealed that PKA/KIN-1 regulates the expression of a set of antimicrobial effectors in the non-neuron tissues, which are required for innate immune responses to S. enterica. Furthermore, PKA/KIN-1 regulated the expression of lysosomal genes during S. enterica infection. Our results suggest that the lysosomal signaling molecules are involved in autophagy by controlling autophagic flux, rather than formation of autophagosomes. As autophagy is crucial for host defense against S. enterica infection in a metazoan, the lysosomal pathway also acts as a downstream effector of the PKA/KIN-1 signaling for innate immunity. Our data indicate that the PKA pathway contributes to innate immunity in C. elegans by signaling from the nervous system to periphery tissues to protect the host against pathogens.

scholarly journals Octopaminergic Signaling Mediates Neural Regulation of Innate Immunity in Caenorhabditis elegans

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Durai Sellegounder ◽  
Chung-Hsiang Yuan ◽  
Phillip Wibisono ◽  
Yiyong Liu ◽  
Jingru Sun
Keyword(s):  
Innate Immunity ◽  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Immune Responses ◽  
Human Health ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Pathogen Infection ◽  
Content Type ◽  
Immunological Homeostasis

ABSTRACT Upon pathogen infection, the nervous system regulates innate immunity to confer coordinated protection to the host. However, the precise mechanisms of such regulation remain unclear. Previous studies have demonstrated that OCTR-1, a putative G protein-coupled receptor for catecholamine, functions in the sensory neurons designated “ASH” to suppress innate immune responses in Caenorhabditis elegans. It is unknown what molecules act as OCTR-1 ligands in the neural immune regulatory circuit. Here we identify neurotransmitter octopamine (OA) as an endogenous ligand for OCTR-1 in immune regulation and show that the OA-producing RIC neurons function in the OCTR-1 neural circuit to suppress innate immunity. RIC neurons are deactivated in the presence of pathogens but transiently activated by nonpathogenic bacteria. Our data support a model whereby an octopaminergic immunoinhibitory pathway is tonically active under normal conditions to maintain immunological homeostasis or suppress unwanted innate immune responses but downregulated upon pathogen infection to allow enhanced innate immunity. As excessive innate immune responses have been linked to a myriad of human health concerns, our study could potentially benefit the development of more-effective treatments for innate immune disorders. IMPORTANCE Insufficient or excessive immune responses to pathogen infection are major causes of disease. Increasing evidence indicates that the nervous system regulates the immune system to help maintain immunological homeostasis. However, the precise mechanisms of this regulation are largely unknown. Here we show the existence of an octopaminergic immunoinhibitory pathway in Caenorhabditis elegans. Our study results indicate that this pathway is tonically active under normal conditions to maintain immunological homeostasis or suppress unwanted innate immune responses but downregulated upon pathogen infection to allow enhanced innate immunity. As excessive innate immune responses have been linked to human health conditions such as Crohn's disease, rheumatoid arthritis, atherosclerosis, diabetes, and Alzheimer's disease, elucidating octopaminergic neural regulation of innate immunity could be helpful in the development of new treatments for innate immune diseases.

scholarly journals The neuropeptide receptor NMUR-1 regulates the specificity of C. elegans innate immunity against pathogen infection

2021 ◽  
Author(s):  
Phillip Wibisono ◽  
Shawndra Wibisono ◽  
Jan Watteyne ◽  
Chia-Hui Chen ◽  
Durai Sellegounder ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Immune Responses ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Immune Genes ◽  
C Elegans ◽  
Adaptive Immune ◽  
Functional Assays

A key question in current immunology is how the innate immune system generates high levels of specificity. Like most invertebrates, Caenorhabditis elegans does not have an adaptive immune system and relies solely on innate immunity to defend itself against pathogen attacks, yet it can still differentiate different pathogens and launch distinct innate immune responses. Here, we have found that functional loss of NMUR-1, a neuronal GPCR homologous to mammalian receptors for the neuropeptide neuromedin U, has diverse effects on C. elegans survival against various bacterial pathogens. Transcriptomic analyses and functional assays revealed that NMUR-1 modulates C. elegans transcription activity by regulating the expression of transcription factors, which, in turn, controls the expression of distinct immune genes in response to different pathogens. Our study has uncovered a molecular basis for the specificity of C. elegans innate immunity that could provide mechanistic insights into understanding the specificity of vertebrate innate immunity.

An integrated view of innate immune mechanisms in C. elegans

2021 ◽  
Author(s):  
Benjamin W. Harding ◽  
Jonathan J. Ewbank
Keyword(s):  
Innate Immune ◽  
Innate Immune Responses ◽  
Fully Integrated ◽  
Immune Mechanisms ◽  
C Elegans ◽  
Cellular Processes ◽  
Physiological Processes ◽  
Model Animal ◽  
Molecular Specificity ◽  
Simple Notion

The simple notion ‘infection causes an immune response' is being progressively refined as it becomes clear that immune mechanisms cannot be understood in isolation, but need to be considered in a more global context with other cellular and physiological processes. In part, this reflects the deployment by pathogens of virulence factors that target diverse cellular processes, such as translation or mitochondrial respiration, often with great molecular specificity. It also reflects molecular cross-talk between a broad range of host signalling pathways. Studies with the model animal C. elegans have uncovered a range of examples wherein innate immune responses are intimately connected with different homeostatic mechanisms, and can influence reproduction, ageing and neurodegeneration, as well as various other aspects of its biology. Here we provide a short overview of a number of such connections, highlighting recent discoveries that further the construction of a fully integrated view of innate immunity.

scholarly journals Mitochondria surveillance systems trigger innate immune responses to bacterial pathogens via AMPK pathway in C. elegans

2020 ◽  
Author(s):  
Shouyong Ju ◽  
Hanqiao Chen ◽  
Shaoying Wang ◽  
Jian Lin ◽  
Raffi V Aroian ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Innate Immune ◽  
Surveillance Systems ◽  
Innate Immune Responses ◽  
Energy Status ◽  
Microbial Infection ◽  
C Elegans ◽  
Host Interaction ◽  
Intracellular Energy

AbstractPathogen recognition and triggering pattern of host innate immune system is critical to understanding pathogen-host interaction. It is generally accepted that the microbial infection can be recognized by host via pattern-triggered immunity (PTI) or effector-triggered immunity (ETI) responses. Recently, non-PRR-mediated cellular surveillance systems have been reported as an important supplement strategy to PTI and ETI responses. However, the mechanism of how surveillance systems sense pathogens and trigger innate immune responses is largely unknown. In the present study, using Bacillus thuringiensis-Caenorhabditis elegans as a model, we found a new approach for surveillance systems to sense the pathogens through no-PPRs patterns. We reported C. elegans can monitor intracellular energy status through the mitochondrial surveillance system to triggered innate immune responses against pathogenic attack via AMP-activated protein kinase (AMPK). Consider that the mitochondria surveillance systems and AMPK are conserved components from worms to mammals, our study suggests that disrupting mitochondrial homeostasis to activate the immune system through AMPK-dependent pathways may widely existing in animals.

Introns encode dsRNAs undetected by RIG-I/MDA5/interferons and sensed via RNase L

2021 ◽  
Vol 118 (46) ◽  
pp. e2102134118
Author(s):  
Alisha Chitrakar ◽  
Kristina Solorio-Kirpichyan ◽  
Eliza Prangley ◽  
Sneha Rath ◽  
Jin Du ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Innate Immune ◽  
Rna Decay ◽  
Antiviral Defense ◽  
Rnase L ◽  
Innate Immune Responses ◽  
Double Stranded Rna ◽  
Turn On ◽  
Nuclear Rna

Double-stranded RNA (dsRNA), a hallmark viral material that activates antiviral interferon (IFN) responses, can appear in human cells also in the absence of viruses. We identify phosphorothioate DNAs (PS DNAs) as triggers of such endogenous dsRNA (endo-dsRNA). PS DNAs inhibit decay of nuclear RNAs and induce endo-dsRNA via accumulation of high levels of intronic and intergenic inverted retroelements (IIIR). IIIRs activate endo-dsRNA responses distinct from antiviral defense programs. IIIRs do not turn on transcriptional RIG-I/MDA5/IFN signaling, but they trigger the dsRNA-sensing pathways of OAS3/RNase L and PKR. Thus, nuclear RNA decay and nuclear-cytosolic RNA sorting actively protect from these innate immune responses to self. Our data suggest that the OAS3/RNase L and PKR arms of innate immunity diverge from antiviral IFN responses and monitor nuclear RNA decay by sensing cytosolic escape of IIIRs. OAS3 provides a receptor for IIIRs, whereas RNase L cleaves IIIR-carrying introns and intergenic RNAs.

scholarly journals Caenorhabditis elegans saposin-like spp-9 is involved in specific innate immune responses

2020 ◽  
Vol 21 (5) ◽  
pp. 301-310
Author(s):  
Bhoomi Madhu ◽  
Mohammed Farhan Lakdawala ◽  
Neethu G. Issac ◽  
Tina L. Gumienny
Keyword(s):  
Caenorhabditis Elegans ◽  
Immune Responses ◽  
Innate Immune ◽  
Innate Immune Responses

scholarly journals Nuclear Hormone Receptor Regulation of MicroRNAs Controls Innate Immune Responses in C. elegans

2013 ◽  
Vol 9 (8) ◽  
pp. e1003545 ◽  
Author(s):  
Feng Liu ◽  
Chen-Xi He ◽  
Li-Jun Luo ◽  
Quan-Li Zou ◽  
Yong-Xu Zhao ◽  
...  
Keyword(s):  
Immune Responses ◽  
Hormone Receptor ◽  
Nuclear Hormone Receptor ◽  
Innate Immune ◽  
Receptor Regulation ◽  
Innate Immune Responses ◽  
C Elegans

scholarly journals Flagellin from Recombinant Attenuated Salmonella enterica Serovar Typhimurium Reveals a Fundamental Role in Chicken Innate Immunity

2012 ◽  
Vol 19 (3) ◽  
pp. 304-312 ◽  
Author(s):  
Zhiming Pan ◽  
Qiuxia Cong ◽  
Shizhong Geng ◽  
Qiang Fang ◽  
Xilong Kang ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Salmonella Enterica ◽  
Rational Design ◽  
Bacterial Load ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Content Type ◽  
Serovar Typhimurium

ABSTRACTRecombinant attenuatedSalmonellavaccines have been extensively studied, with a focus on eliciting specific immune responses against foreign antigens. However, very little is known about the innate immune responses, particularly the role of flagellin, in the induction of innate immunity triggered by recombinant attenuatedSalmonellain chickens. In the present report, we describe twoSalmonella entericaserovar Typhimurium vaccine strains, wild-type (WT) or flagellin-deficient (flhD)Salmonella, both expressing the fusion protein (F) gene of Newcastle disease virus. We examined the bacterial load and spatiotemporal kinetics of expression of inflammatory cytokine, chemokine, and Toll-like receptor 5 (TLR5) genes in the cecum, spleen, liver, and heterophils following oral immunization of chickens with the twoSalmonellastrains. TheflhDmutant exhibited an enhanced ability to establish systemic infection compared to the WT. In contrast, the WT strain induced higher levels of interleukin-1β (IL-1β), CXCLi2, and TLR5 mRNAs in cecum, the spleen, and the heterophils than theflhDmutant at different times postinfection. Collectively, the present data reveal a fundamental role of flagellin in the innate immune responses induced by recombinant attenuatedSalmonellavaccines in chickens that should be considered for the rational design of novel vaccines for poultry.

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