Mast cell specific receptor Mrgprb2/X2 regulates bladder immunity during urinary tract infections

Mast cell specific receptor Mrgprb2/X2 regulates bladder immunity during urinary tract infections | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Mast cell specific receptor Mrgprb2/X2 regulates bladder immunity during urinary tract infections Xintong Dong, Waris Muhammad Khuwaja, Zahra Janjua, Nicole De Nisco, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9076947/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Urinary tract infections (UTIs) are the most common bacterial infections in women. During UTI, the host mounts a rapid immune response to clear the invading pathogen. Mast cells are tissue resident immune cells found in the bladder lamina propria and can serve as first responders to bacterial infections. We investigated the role of the mouse mast cell receptor Mrgprb2 and its human homologue MRGPRX2 in UTI. During acute UTI, Mrgprb2 is activated by the antimicrobial peptide cathelicidin and mediates mast cell degranulation. Using Mrgprb2 knockout mice, we demonstrated that Mrgprb2 promotes immune cell recruitment and amplifies inflammation, leading to epithelial damage and increased bacterial burden. Pharmacological inhibition of Mrgprb2 with its antagonist osthole improved infection outcomes. Using a humanized MRGPRX2 knock-in mouse, we show conserved functions of the mouse and human receptors in the bladder. Our findings identify human MRGPRX2 as a potential therapeutic target to improve UTI patient outcomes. Biological sciences/Immunology/Infectious diseases/Bacterial infection Biological sciences/Immunology/Innate immune cells/Granulocytes/Mast cells Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Supplementmergedupdated.pdf Supplemental figures and legends Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9076947","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":607726345,"identity":"f34a42f2-1b5b-4192-9346-b7bbf25d4738","order_by":0,"name":"Xintong 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During UTI, the host mounts a rapid immune response to clear the invading pathogen. Mast cells are tissue resident immune cells found in the bladder lamina propria and can serve as first responders to bacterial infections. We investigated the role of the mouse mast cell receptor Mrgprb2 and its human homologue MRGPRX2 in UTI. During acute UTI, Mrgprb2 is activated by the antimicrobial peptide cathelicidin and mediates mast cell degranulation. Using Mrgprb2 knockout mice, we demonstrated that Mrgprb2 promotes immune cell recruitment and amplifies inflammation, leading to epithelial damage and increased bacterial burden. Pharmacological inhibition of Mrgprb2 with its antagonist osthole improved infection outcomes. Using a humanized MRGPRX2 knock-in mouse, we show conserved functions of the mouse and human receptors in the bladder. 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