scholarly journals Microtubule plus-end dynamics link wound repair to the innate immune response

2019 ◽  
Author(s):  
Clara Taffoni ◽  
Shizue Omi ◽  
Caroline Huber ◽  
Sebastien Mailfert ◽  
Matthieu Fallet ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Wound Repair ◽  
Wound Closure ◽  
Immune Reaction ◽  
Innate Immune ◽  
First Line ◽  
Physical Damage ◽  
Wound Site ◽  
C Elegans

AbstractAs a first line of defence against the environment, the epidermis protect animals from infection and physical damage. In C. elegans, wounding the epidermal epithelium triggers both an immune reaction and a repair response. Exactly how these are controlled, and the degree to which they are inter-connected remains unclear. To address these questions, we established a simple system for simultaneously inflicting precise laser wounds and imaging at high spatial and temporal resolution. We show that in C. elegans, wounding provokes a rapid sealing of the plasma membrane, involving reorganisation of phosphatidylinositol 4,5- bisphosphate domains. This is followed by a radial recruitment at the wound site of EBP-2/EB1, a protein that binds the plus ends of microtubules. EB1 recruitment is accompanied by a reorganisation of microtubules, required for the subsequent recruitment of actin and wound closure. It is also required for the directed trafficking towards the site of injury of the key signalling protein SNF-12. In the absence of SNF-12 recruitment, there is an abrogation of the immune response. Our results suggest that microtubule dynamics coordinate the cytoskeletal changes required for wound repair and the concomitant activation of the innate immune response.

scholarly journals Microtubule plus-end dynamics link wound repair to the innate immune response

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Clara Taffoni ◽  
Shizue Omi ◽  
Caroline Huber ◽  
Sébastien Mailfert ◽  
Mathieu Fallet ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Plasma Membrane ◽  
Wound Repair ◽  
Immune Reaction ◽  
Microtubule Dynamics ◽  
Innate Immune ◽  
Physical Damage ◽  
Actin Ring ◽  
Injury Site

The skin protects animals from infection and physical damage. In Caenorhabditis elegans, wounding the epidermis triggers an immune reaction and a repair response, but it is not clear how these are coordinated. Previous work implicated the microtubule cytoskeleton in the maintenance of epidermal integrity (Chuang et al., 2016). Here, by establishing a simple wounding system, we show that wounding provokes a reorganisation of plasma membrane subdomains. This is followed by recruitment of the microtubule plus end-binding protein EB1/EBP-2 around the wound and actin ring formation, dependent on ARP2/3 branched actin polymerisation. We show that microtubule dynamics are required for the recruitment and closure of the actin ring, and for the trafficking of the key signalling protein SLC6/SNF-12 toward the injury site. Without SNF-12 recruitment, there is an abrogation of the immune response. Our results suggest that microtubule dynamics coordinate the cytoskeletal changes required for wound repair and the concomitant activation of innate immunity.

scholarly journals Mitochondrial UPR negatively regulates wounding-induced innate immune response in C. elegans epidermis

2021 ◽  
Author(s):  
Jianzhi Zhao ◽  
Hongying Fu ◽  
Hengda Zhou ◽  
Xuecong Ren ◽  
Yuanyuan Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Signaling Pathways ◽  
Innate Immune Response ◽  
Tissue Damage ◽  
P38 Map Kinase ◽  
Innate Immune ◽  
Loss Of Function ◽  
C Elegans ◽  
Unfolded Protein ◽  
Protein Response

Tissue damage elicits a rapid innate immune response that is essential for efficient wound healing and survival of metazoans. It is well known that p38 MAPK kinase, TGF-β, and hemidesmosome signaling pathways have been involved in wounding-induced innate immunity in C. elegans. Here, we find that loss of function of ATFS-1 increased innate immune response while an elevated level of mitochondrial unfolded protein response (mitoUPR) inhibits the innate immune response upon epidermal wounding. Epidermal wounding triggers the nucleus export of ATFS-1 and inhibits themitoUPR in C. elegans epidermis. Moreover, genetic analysis suggests that ATFS-1 functions upstream of the p38 MAP kinase, TGF-β, and DAF-16 signaling pathways in regulating AMPs induction. Thus, our results suggest that the mitoUPR function as an intracellular signal required to fine-tune innate immune response after tissue damage.

scholarly journals Lifespan Extension in C. elegans Caused by Bacterial Colonization of the Intestine and Subsequent Activation of an Innate Immune Response

2019 ◽  
Vol 49 (1) ◽  
pp. 100-117.e6 ◽  
Author(s):  
Sandeep Kumar ◽  
Brian M. Egan ◽  
Zuzana Kocsisova ◽  
Daniel L. Schneider ◽  
John T. Murphy ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Bacterial Colonization ◽  
Innate Immune ◽  
Lifespan Extension ◽  
C Elegans ◽  
Subsequent Activation

Loss of DNase II function in the gonad is associated with a higher expression of antimicrobial genes in Caenorhabditis elegans

2015 ◽  
Vol 470 (1) ◽  
pp. 145-154 ◽  
Author(s):  
Hsiang Yu ◽  
Huey-Jen Lai ◽  
Tai-Wei Lin ◽  
Chang-Shi Chen ◽  
Szecheng J. Lo
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Caenorhabditis Elegans ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Dnase Ii ◽  
C Elegans ◽  
Elevated Expression

This study uncovered NUC-1 and CRN-7 function in germline apoptosis. Mutations of nuc-1 and crn-7 led to elevated expression of five innate-immunity-related genes and demonstrated that DNase II activity is associated with an innate immune response in C. elegans.

scholarly journals Analysis of the Caenorhabditis elegans innate immune response to Coxiella burnetii

2016 ◽  
Vol 23 (2) ◽  
pp. 111-127 ◽  
Author(s):  
James M Battisti ◽  
Lance A Watson ◽  
Myo T Naung ◽  
Adam M Drobish ◽  
Ekaterina Voronina ◽  
...  
Keyword(s):  
Immune Response ◽  
Caenorhabditis Elegans ◽  
Innate Immune Response ◽  
Coxiella Burnetii ◽  
Molecular Mechanisms ◽  
Q Fever ◽  
Innate Immune ◽  
Human Pathogens ◽  
C Elegans ◽  
Intestinal Distension

The nematode Caenorhabditis elegans is well established as a system for characterization and discovery of molecular mechanisms mediating microbe-specific inducible innate immune responses to human pathogens. Coxiella burnetii is an obligate intracellular bacterium that causes a flu-like syndrome in humans (Q fever), as well as abortions in domesticated livestock, worldwide. Initially, when wild type C. elegans (N2 strain) was exposed to mCherry-expressing C. burnetii (CCB) a number of overt pathological manifestations resulted, including intestinal distension, deformed anal region and a decreased lifespan. However, nematodes fed autoclave-killed CCB did not exhibit these symptoms. Although vertebrates detect C. burnetii via TLRs, pathologies in tol-1(–) mutant nematodes were indistinguishable from N2, and indicate nematodes do not employ this orthologue for detection of C. burnetii. sek-1(–) MAP kinase mutant nematodes succumbed to infection faster, suggesting that this signaling pathway plays a role in immune activation, as previously shown for orthologues in vertebrates during a C. burnetii infection. C. elegans daf-2(–) mutants are hyper-immune and exhibited significantly reduced pathological consequences during challenge. Collectively, these results demonstrate the utility of C. elegans for studying the innate immune response against C. burnetii and could lead to discovery of novel methods for prevention and treatment of disease in humans and livestock.

scholarly journals Heat shock enhances innate immune response to PG‐PS and M. tuberculosis in C. elegans

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Krishnaswamy Kannan ◽  
Xiaoxiao Wan ◽  
Aarthi Kannan ◽  
Deyu Fang ◽  
Robert Ortmann
Keyword(s):  
Immune Response ◽  
Heat Shock ◽  
Innate Immune Response ◽  
Innate Immune ◽  
C Elegans

scholarly journals Structural Damage in the C. elegans Epidermis Causes Release of STA-2 and Induction of an Innate Immune Response

Immunity ◽  
2015 ◽  
Vol 42 (2) ◽  
pp. 309-320 ◽  
Author(s):  
Yun Zhang ◽  
Wenna Li ◽  
Linfeng Li ◽  
Yuanbao Li ◽  
Rong Fu ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Structural Damage ◽  
Innate Immune ◽  
C Elegans

scholarly journals Gene expression variability across cells and species shapes innate immunity

2017 ◽  
Author(s):  
Tzachi Hagai ◽  
Xi Chen ◽  
Ricardo J Miragaia ◽  
Tomás Gomes ◽  
Raghd Rostom ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Innate Immunity ◽  
Innate Immune Response ◽  
Innate Immune ◽  
First Line ◽  
Expression Variability ◽  
Cytokines And Chemokines ◽  
Cell To Cell Variability ◽  
Unique Expression Pattern

SummaryAs the first line of defence against pathogens, cells mount an innate immune response, which is highly variable from cell to cell. The response must be potent yet carefully controlled to avoid self-damage. How these constraints have shaped the evolution of innate immunity remains poorly understood. Here, we characterise this programme’s transcriptional divergence between species and expression variability across cells. Using bulk and single-cell transcriptomics in primate and rodent fibroblasts challenged with an immune stimulus, we reveal a striking architecture of the innate immune response. Rapidly diverging genes, including cytokines and chemokines, also vary across cells and have distinct promoter structures. Conversely, genes involved in response regulation, such as transcription factors and kinases, are conserved between species and display low cell-to-cell variability. We suggest that this unique expression pattern, observed across species and conditions, has evolved as a mechanism for fine-tuned regulation, to achieve an effective but balanced response.

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