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 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 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.

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.

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 Shaping of Innate Immune Response by Fatty Acid Metabolite Palmitate

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1633 ◽  
Author(s):  
Hong-Tai Tzeng ◽  
I-Tsu Chyuan ◽  
Wei-Yu Chen
Keyword(s):  
Innate Immunity ◽  
Immune Cells ◽  
Immune Cell ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Innate Immune Responses ◽  
Fatty Acid Metabolite ◽  
Physiological Processes ◽  
Protein Palmitoylation ◽  
Inflammatory Processes

Innate immune cells monitor invading pathogens and pose the first-line inflammatory response to coordinate with adaptive immunity for infection removal. Innate immunity also plays pivotal roles in injury-induced tissue remodeling and the maintenance of tissue homeostasis in physiological and pathological conditions. Lipid metabolites are emerging as the key players in the regulation of innate immune responses, and recent work has highlighted the importance of the lipid metabolite palmitate as an essential component in this regulation. Palmitate modulates innate immunity not only by regulating the activation of pattern recognition receptors in local innate immune cells, but also via coordinating immunological activity in inflammatory tissues. Moreover, protein palmitoylation controls various cellular physiological processes. Herein, we review the updated evidence that palmitate catabolism contributes to innate immune cell-mediated inflammatory processes that result in immunometabolic disorders.

scholarly journals C. elegans monitor energy status to trigger innate immune responses via AMPK pathway against bacterial pathogens

2021 ◽  
Author(s):  
Donghai Peng ◽  
Shouyong Ju ◽  
Hanqiao Chen ◽  
Shaoying Wang ◽  
Jian Lin ◽  
...  
Keyword(s):  
Bacillus Thuringiensis ◽  
Immune Responses ◽  
Surveillance System ◽  
Innate Immune ◽  
Ion Leakage ◽  
Surveillance Systems ◽  
Innate Immune Responses ◽  
Energy Status ◽  
Microbial Infection ◽  
C Elegans

Abstract Pathogen recognition and triggering pattern of host innate immune system is critical to understanding pathogen-host interaction. Cellular surveillance systems have been reported as an important strategy for the identification of microbial infection. In the present study, using Bacillus thuringiensis-Caenorhabditis elegans as a model, we found a new approach for surveillance systems to sense the pathogens. We report that Bacillus thuringiensis produced Cry5Ba, a classical PFTs, leading mitochondrial damage and energy imbalance by causing potassium ion leakage, instead of directly targeting mitochondria. Interestingly, 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). Obviously, it is common that pathogens produce toxins to cause potassium leakage. Our study indicate that the imbalance of energy status is a common result of pathogen infection.Besides. AMPK-dependent surveillance system can act as a new stratege for host to recognize and defense pathogens.

scholarly journals Perturbation of ubiquitin homeostasis promotes macrophage oxidative defenses

2018 ◽  
Author(s):  
Marie-Eve Charbonneau ◽  
Karla D. Passalacqua ◽  
Susan E. Hagen ◽  
Hollis D. Showalter ◽  
Christiane E. Wobus ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Specific Pattern ◽  
Innate Immune ◽  
Signaling Cascades ◽  
Innate Immune Responses ◽  
Post Translational Modification ◽  
Downstream Signaling ◽  
Cellular Processes ◽  
Phagocyte Nadph Oxidase ◽  
Protein Ubiquitination

Innate immune responses rely on specific pattern recognition receptors that induce downstream signaling cascades and promote inflammatory responses. Emerging evidence suggests that cells may also recognize alterations in cellular processes induced by infection. Protein ubiquitination is a post-translational modification essential for maintaining cellular homeostasis, and infection can cause global alterations in the host ubiquitin proteome. Here we used a chemical biology approach to perturb the cellular ubiquitin proteome as a simplified model to study the direct effect of ubiquitin homeostasis on macrophage responses. We show that perturbation of ubiquitin homeostasis results in a rapid and transient burst of reactive oxygen species (ROS) that promotes macrophage anti-infective capacity. ROS production was dependent on the activity of the phagocyte NADPH oxidase NOX2 and was associated with an increase in intracellular calcium. Our findings suggest that major changes in the host ubiquitin landscape may be a potent signal to rapidly deploy innate immune defenses.

Granulocyte apoptosis in the pathogenesis and resolution of lung disease

2006 ◽  
Vol 110 (3) ◽  
pp. 293-304 ◽  
Author(s):  
Stephen M. Bianchi ◽  
David H. Dockrell ◽  
Stephen A. Renshaw ◽  
Ian Sabroe ◽  
Moira K. B. Whyte
Keyword(s):  
Immune Responses ◽  
Lung Disease ◽  
Inflammatory Cell ◽  
Control Point ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Potential Control ◽  
Cellular Processes ◽  
Cell Type Specific ◽  
Eosinophil Granulocytes

Apoptosis, programmed cell death, of neutrophil and eosinophil granulocytes is a potential control point in the physiological resolution of innate immune responses. There is also increasing evidence that cellular processes of apoptosis can be dysregulated by pathogens as a mechanism of immune evasion and that delayed apoptosis, resulting in prolonged inflammatory cell survival, is important in persistence of tissue inflammation. The identification of cell-type specific pathways to apoptosis may allow the design of novel anti-inflammatory therapies or agents to augment the innate immune responses to infection. This review will explore the physiological roles of granulocyte apoptosis and their importance in infectious and non-infectious lung disease.

scholarly journals Distinct Innate Immune Responses to Infection and Wounding in the C. elegans Epidermis

2008 ◽  
Vol 18 (7) ◽  
pp. 481-489 ◽  
Author(s):  
Nathalie Pujol ◽  
Sophie Cypowyj ◽  
Katja Ziegler ◽  
Anne Millet ◽  
Aline Astrain ◽  
...  
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
C Elegans
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