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.

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 Recent Advances on the Innate Immune Response to Coxiella burnetii

2021 ◽  
Vol 11 ◽  
Author(s):  
Guido Sireci ◽  
Giusto Davide Badami ◽  
Diana Di Liberto ◽  
Valeria Blanda ◽  
Francesca Grippi ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Coxiella Burnetii ◽  
Q Fever ◽  
Cell Types ◽  
Innate Immune ◽  
Host Cells ◽  
Experimental Systems ◽  
Monocytes And Macrophages ◽  
Review Reports

Coxiella burnetii is an obligate intracellular Gram-negative bacterium and the causative agent of a worldwide zoonosis known as Q fever. The pathogen invades monocytes and macrophages, replicating within acidic phagolysosomes and evading host defenses through different immune evasion strategies that are mainly associated with the structure of its lipopolysaccharide. The main transmission routes are aerosols and ingestion of fomites from infected animals. The innate immune system provides the first host defense against the microorganism, and it is crucial to direct the infection towards a self-limiting respiratory disease or the chronic form. This review reports the advances in understanding the mechanisms of innate immunity acting during C. burnetii infection and the strategies that pathogen put in place to infect the host cells and to modify the expression of specific host cell genes in order to subvert cellular processes. The mechanisms through which different cell types with different genetic backgrounds are differently susceptible to C. burnetii intracellular growth are discussed. The subsets of cytokines induced following C. burnetii infection as well as the pathogen influence on an inflammasome-mediated response are also described. Finally, we discuss the use of animal experimental systems for studying the innate immune response against C. burnetii and discovering novel methods for prevention and treatment of disease in humans and livestock.

scholarly journals Caenorhabditis elegans microRNAs of the let-7 family act in innate immune response circuits and confer robust developmental timing against pathogen stress

2015 ◽  
Vol 112 (18) ◽  
pp. E2366-E2375 ◽  
Author(s):  
Zhiji Ren ◽  
Victor R. Ambros
Keyword(s):  
Immune Response ◽  
Caenorhabditis Elegans ◽  
P38 Mapk ◽  
Innate Immune Response ◽  
Regulatory Networks ◽  
Mapk Pathway ◽  
Regulation Of Gene Expression ◽  
Innate Immune ◽  
Developmental Timing ◽  
C Elegans

Animals maintain their developmental robustness against natural stresses through numerous regulatory mechanisms, including the posttranscriptional regulation of gene expression by microRNAs (miRNAs). Caenorhabditis elegans miRNAs of the let-7 family (let-7-Fam) function semiredundantly to confer robust stage specificity of cell fates in the hypodermal seam cell lineages. Here, we show reciprocal regulatory interactions between let-7-Fam miRNAs and the innate immune response pathway in C. elegans. Upon infection of C. elegans larvae with the opportunistic human pathogen Pseudomonas aeruginosa, the developmental timing defects of certain let-7-Fam miRNA mutants are enhanced. This enhancement is mediated by the p38 MAPK innate immune pathway acting in opposition to let-7-Fam miRNA activity, possibly via the downstream Activating Transcription Factor-7 (ATF-7). Furthermore, let-7-Fam miRNAs appear to exert negative regulation on the worm’s resistance to P. aeruginosa infection. Our results show that the inhibition of pathogen resistance by let-7 involves downstream heterochronic genes and the p38 MAPK pathway. These findings suggest that let-7-Fam miRNAs are integrated into innate immunity gene regulatory networks, such that this family of miRNAs modulates immune responses while also ensuring robust timing of developmental events under pathogen stress.

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 Broad Ultrastructural and Transcriptomic Changes Underlie the Multinucleated Giant Hemocyte Mediated Innate Immune Response against Parasitoids

2021 ◽  
pp. 1-20
Author(s):  
Gyöngyi Cinege ◽  
Lilla B. Magyar ◽  
Attila L. Kovács ◽  
Zita Lerner ◽  
Gábor Juhász ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Structural Changes ◽  
Molecular Mechanisms ◽  
Mechanistic Model ◽  
Parasitoid Wasp ◽  
Innate Immune ◽  
Drosophila Ananassae ◽  
Membrane Structures ◽  
Intracytoplasmic Membrane

Multinucleated giant hemocytes (MGHs) represent a novel type of blood cell in insects that participate in a highly efficient immune response against parasitoid wasps involving isolation and killing of the parasite. Previously, we showed that circulating MGHs have high motility and the interaction with the parasitoid rapidly triggers encapsulation. However, structural and molecular mechanisms behind these processes remained elusive. Here, we used detailed ultrastructural analysis and live cell imaging of MGHs to study encapsulation in <i>Drosophila ananassae</i> after parasitoid wasp infection. We found dynamic structural changes, mainly driven by the formation of diverse vesicular systems and newly developed complex intracytoplasmic membrane structures, and abundant generation of giant cell exosomes in MGHs. In addition, we used RNA sequencing to study the transcriptomic profile of MGHs and activated plasmatocytes 72 h after infection, as well as the uninduced blood cells. This revealed that differentiation of MGHs was accompanied by broad changes in gene expression. Consistent with the observed structural changes, transcripts related to vesicular function, cytoskeletal organization, and adhesion were enriched in MGHs. In addition, several orphan genes encoding for hemolysin-like proteins, pore-forming toxins of prokaryotic origin, were expressed at high level, which may be important for parasitoid elimination. Our results reveal coordinated molecular and structural changes in the course of MGH differentiation and parasitoid encapsulation, providing a mechanistic model for a powerful innate immune response.

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

scholarly journals A multiscale signalling network map of innate immune response in cancer reveals cell heterogeneity signatures

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Maria Kondratova ◽  
Urszula Czerwinska ◽  
Nicolas Sompairac ◽  
Sebastian D. Amigorena ◽  
Vassili Soumelis ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Molecular Mechanisms ◽  
Chemical Species ◽  
Suppressor Cells ◽  
Tumour Microenvironment ◽  
Innate Immune ◽  
Literature Mining ◽  
Cell Type ◽  
Signalling Network

Abstract The lack of integrated resources depicting the complexity of the innate immune response in cancer represents a bottleneck for high-throughput data interpretation. To address this challenge, we perform a systematic manual literature mining of molecular mechanisms governing the innate immune response in cancer and represent it as a signalling network map. The cell-type specific signalling maps of macrophages, dendritic cells, myeloid-derived suppressor cells and natural killers are constructed and integrated into a comprehensive meta map of the innate immune response in cancer. The meta-map contains 1466 chemical species as nodes connected by 1084 biochemical reactions, and it is supported by information from 820 articles. The resource helps to interpret single cell RNA-Seq data from macrophages and natural killer cells in metastatic melanoma that reveal different anti- or pro-tumor sub-populations within each cell type. Here, we report a new open source analytic platform that supports data visualisation and interpretation of tumour microenvironment activity in cancer.

Innate Immune Response to Cytoplasmic DNA: Mechanisms and Diseases

2020 ◽  
Vol 38 (1) ◽  
pp. 79-98 ◽  
Author(s):  
Ming-Ming Hu ◽  
Hong-Bing Shu
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Host Defense ◽  
Cyclic Gmp ◽  
Molecular Mechanisms ◽  
Adaptor Protein ◽  
Innate Immune ◽  
Cellular Stress Response ◽  
Cytoplasmic Dna ◽  
Stress Response Pathway

DNA has been known to be a potent immune stimulus for more than half a century. However, the underlying molecular mechanisms of DNA-triggered immune response have remained elusive until recent years. Cyclic GMP-AMP synthase (cGAS) is a major cytoplasmic DNA sensor in various types of cells that detect either invaded foreign DNA or aberrantly located self-DNA. Upon sensing of DNA, cGAS catalyzes the formation of cyclic GMP-AMP (cGAMP), which in turn activates the ER-localized adaptor protein MITA (also named STING) to elicit the innate immune response. The cGAS-MITA axis not only plays a central role in host defense against pathogen-derived DNA but also acts as a cellular stress response pathway by sensing aberrantly located self-DNA, which is linked to the pathogenesis of various human diseases. In this review, we summarize the spatial and temporal mechanisms of host defense to cytoplasmic DNA mediated by the cGAS-MITA axis and discuss the association of malfunctions of this axis with autoimmune and other diseases.

scholarly journals Coxiella burnetii Interaction with Neutrophils and MacrophagesIn Vitroand in SCID Mice following Aerosol Infection

2013 ◽  
Vol 81 (12) ◽  
pp. 4604-4614 ◽  
Author(s):  
Alexandra Elliott ◽  
Ying Peng ◽  
Guoquan Zhang
Keyword(s):  
Immune Response ◽  
Coxiella Burnetii ◽  
Q Fever ◽  
Natural Infection ◽  
Scid Mice ◽  
Innate Immune ◽  
Content Type ◽  
Aerosol Infection

ABSTRACTCoxiella burnetiiis an obligate intracellular bacterium that causes acute and chronic Q fever in humans. Human Q fever is mainly transmitted by aerosol infection. However, there is a fundamental gap in the knowledge regarding the mechanisms of pulmonary immunity againstC. burnetiiinfection. This study focused on understanding the interaction betweenC. burnetiiand innate immune cellsin vitroandin vivo. Both virulentC. burnetiiNine Mile phase I (NMI) and avirulent Nine Mile phase II (NMII) were able to infect neutrophils, while the infection rates were lower than 29%, suggesting thatC. burnetiican infect neutrophils, but infection is limited. Interestingly,C. burnetiiinside neutrophils can infect and replicate within macrophages, suggesting that neutrophils cannot killC. burnetiiandC. burnetiimay be using infection of neutrophils as an evasive strategy to infect macrophages. To elucidate the mechanisms of the innate immune response toC. burnetiinatural infection, SCID mice were exposed to aerosolizedC. burnetii. Surprisingly, neutrophil influx into the lungs was delayed until day 7 postinfection in both NMI- and NMII-infected mice. This result suggests that neutrophils may play a unique role in the early immune response against aerosolizedC. burnetii. Studying the interaction betweenC. burnetiiand the innate immune system can provide a model system for understanding how the bacteria evade early immune responses to cause infection.

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