Tick peptides evoke itch by activating MrgprC11/MRGPRX1 to sensitize TRPV1 in pruriceptors

Li, Xueke; Yang, Haifeng; Han, Yuewen; Yin, Shen; Shen, Bingzheng; Wu, Yingliang; Li, Wenxin; Cao, Zhijian

doi:10.1016/j.jaci.2020.12.626

Cited by 30 publications

(21 citation statements)

References 42 publications

(51 reference statements)

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“…IPDef1 initiated itch through activating MrgprC11/X1 to sensitize downstream ion channel TRPV1 on dorsal root ganglion neurons. Intriguingly, IPDef1 was also reported to trigger MrgprB2/X2 expressed on mast cells, leading to inflammatory cytokine release and provoking acute inflammation in mice [ 90 ]. These new findings extend the function of tick defensins to itch induction, which provides the basis for the precaution and treatment of pruritus caused by the stings or bites of arthropods.…”

Section: Discussionmentioning

confidence: 99%

Defensins as a promising class of tick antimicrobial peptides: a scoping review

Zhou

Chen

et al. 2022

Infect Dis Poverty

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Background Ticks are hematophagous parasites that transmit an extensive range of pathogens to their vertebrate hosts. Ticks can destroy invading microorganisms or alleviate infection via their rudimentary but orchestrated innate immune system. Antimicrobial peptides (AMPs) are important components of tick innate immunity. Among these humoral effector molecules, defensins are well-studied and widely identified in various species of Ixodidae (hard ticks) and Argasidae (soft ticks). This review was aimed at presenting the characterization of tick defensins from structure-based taxonomic status to antimicrobial function. Main text All published papers written in English from 2001 to May 2022 were searched through PubMed and Web of Science databases with the combination of relevant terms on tick defensins. Reports on identification and characterization of tick defensins were included. Of the 329 entries retrieved, 57 articles were finally eligible for our scoping review. Tick defensins mainly belong to the antibacterial ancient invertebrate-type defensins of the cis-defensins superfamily. They are generally small, cationic, and amphipathic, with six cysteine residues forming three intra-molecular disulfide bonds. Tick defensins primarily target membranes of a variety of pathogens, including Gram-positive and Gram-negative bacteria, fungi, viruses, and protozoa. Since tick defensins have a high degree of variability, we summarize their common biological properties and enumerate representative peptides. Along with the various and potent antimicrobial activities, the role of tick defensins in determining vector competence is discussed. Conclusions Due to their broad-spectrum antimicrobial activities, tick defensins are considered novel candidates or targets for controlling infectious diseases. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Defensins as a promising class of tick antimicrobial peptides: a scoping review

Zhou

Chen

et al. 2022

Infect Dis Poverty

View full text Add to dashboard Cite

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“…It was observed that patients who received Ruxolitinib had a faster clinical and chest CT improvement and displayed significantly decreased levels of cytokines compared to control group. Moreover, no deaths were recorded in the Ruxolitinib receiving group (n = 20) while three patients died due to respiratory failure in the control group (n = 21) [ 94 ]. Another JAKi, Baricitinib has been suggested to be of therapeutic use against SARS-CoV-2 [ 95 ].…”

Section: Anti-il-6 Agents: Therapeutic Targets For Covid-19 Infectionmentioning

confidence: 99%

Interleukin-6 Perpetrator of the COVID-19 Cytokine Storm

et al. 2021

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COVID-19 has emerged as a global pandemic. It is mainly manifested as pneumonia which may deteriorate into severe respiratory failure. The major hallmark of the disease is the systemic inflammatory immune response characterized by Cytokine Storm (CS). CS is marked by elevated levels of inflammatory cytokines, mainly interleukin-6 (IL-6), IL-8, IL-10, tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Of these, IL-6 is found to be significantly associated with higher mortality. IL-6 is also a robust marker for predicting disease prognosis and deterioration of clinical profile. In this review, the pivotal role played by IL-6 in the immuno-pathology of COVID-19 has been illustrated. The role of IL-6 as a pleiotropic cytokine executing both pro and anti-inflammatory activities has been reviewed. ADAM 10, a metalloproteinase switches the anti-inflammatory pathway of IL-6 to pro inflammatory hence blocking the action of ADAM 10 could be a new therapeutic strategy to mitigate the proinflammatory action of IL-6. Furthermore, we explore the role of anti-IL6 agents, IL-6 receptor antibodies which were being used for autoimmune diseases but now are being repurposed for the therapy of COVID-19.

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“…Many of the Mrgprs exhibited preferential distribution exclusively in peripheral sensory neurons. Several of the Mrgprs have been identified to be receptors for itch and pain, including MrgprA3, MrgprC11, and MrgprD [33,51]. In this study, we screened the gene expression of all members of the Mrgprs family in DRG from ACD model mice by RNA-seq and found that Mrgpra3, Mrgprc11, and Mrgprd showed significant upregulation.…”

Section: Discussionmentioning

confidence: 97%

Exploring neuronal mechanisms involved in the scratching behavior of a mouse model of allergic contact dermatitis by transcriptomics

et al. 2022

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Background Allergic contact dermatitis (ACD) is a common skin condition characterized by contact hypersensitivity to allergens, accompanied with skin inflammation and a mixed itch and pain sensation. The itch and pain dramatically affects patients’ quality of life. However, still little is known about the mechanisms triggering pain and itch sensations in ACD. Methods We established a mouse model of ACD by sensitization and repetitive challenge with the hapten oxazolone. Skin pathological analysis, transcriptome RNA sequencing (RNA-seq), qPCR, Ca2+ imaging, immunostaining, and behavioral assay were used for identifying gene expression changes in dorsal root ganglion innervating the inflamed skin of ACD model mice and for further functional validations. Results The model mice developed typical ACD symptoms, including skin dryness, erythema, excoriation, edema, epidermal hyperplasia, inflammatory cell infiltration, and scratching behavior, accompanied with development of eczematous lesions. Transcriptome RNA-seq revealed a number of differentially expressed genes (DEGs), including 1436-DEG mRNAs and 374-DEG-long noncoding RNAs (lncRNAs). We identified a number of DEGs specifically related to sensory neuron signal transduction, pain, itch, and neuroinflammation. Comparison of our dataset with another published dataset of atopic dermatitis mouse model identified a core set of genes in peripheral sensory neurons that are exclusively affected by local skin inflammation. We further found that the expression of the pain and itch receptor MrgprD was functionally upregulated in dorsal root ganglia (DRG) neurons innervating the inflamed skin of ACD model mice. MrgprD activation induced by its agonist β-alanine resulted in exaggerated scratching responses in ACD model mice compared with naïve mice. Conclusions We identified the molecular changes and cellular pathways in peripheral sensory ganglia during ACD that might participate in neurogenic inflammation, pain, and itch. We further revealed that the pain and itch receptor MrgprD is functionally upregulated in DRG neurons, which might contribute to peripheral pain and itch sensitization during ACD. Thus, targeting MrgprD may be an effective method for alleviating itch and pain in ACD.

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Tick peptides evoke itch by activating MrgprC11/MRGPRX1 to sensitize TRPV1 in pruriceptors

Cited by 30 publications

References 42 publications

Defensins as a promising class of tick antimicrobial peptides: a scoping review

Defensins as a promising class of tick antimicrobial peptides: a scoping review

Interleukin-6 Perpetrator of the COVID-19 Cytokine Storm

Exploring neuronal mechanisms involved in the scratching behavior of a mouse model of allergic contact dermatitis by transcriptomics

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