{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T18:15:58Z","timestamp":1778523358710,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013520","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000}}],"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001246","name":"Ambrose Monell Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI068932"],"award-info":[{"award-number":["R01AI068932"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI139525"],"award-info":[{"award-number":["R01AI139525"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI129819"],"award-info":[{"award-number":["R01AI129819"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21AI163969"],"award-info":[{"award-number":["R21AI163969"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21AI163969"],"award-info":[{"award-number":["R21AI163969"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Peptidoglycan Recognition Proteins (PGRPs) are conserved proteins regulating immune responses to the peptidoglycan microbe-associated molecular patterns (MAMPs). Compared to other dipterans, the tsetse fly (\n                    <jats:italic>Glossina morsitans morsitans<\/jats:italic>\n                    ) genome encodes only five PGRPs- PGRP-LA, -LB, -LC, -SA, and -SB \u2013 far fewer than most dipterans, likely reflecting its sterile blood diet and streamlined microbiota. Here, we identify PGRP-LA as a critical regulator of peritrophic matrix (PM) integrity in the cardia (proventriculus), the tissue responsible for PM production. The PM is a chitinous sleeve-like barrier that separates the midgut epithelium from the ingested bloodmeal, supporting digestive homeostasis and infection resistance. We show that\n                    <jats:italic>pgrp-la<\/jats:italic>\n                    is prominently expressed in the cardia, transiently induced after a bloodmeal in newly eclosed flies, and reinduced following subsequent feedings, likely in response to blood- constituents or mechanical stretch. This induction is sustained during microbial exposure and prolonged in trypanosome-infected flies. RNAi-mediated reduction of\n                    <jats:italic>pgrp-la<\/jats:italic>\n                    significantly increased the prevalence of midgut trypanosome infections, indicating a protective role during early infection. PGRP-LA did not mediate infection resistance via canonical IMD pathway signaling, as its silencing did not affect antimicrobial peptide expression. Instead, PGRP-LA modulated the expression of PM-associated genes and gut barrier integrity. Silencing\n                    <jats:italic>pgrp-la<\/jats:italic>\n                    reduced PM structure, increased midgut weights and enhanced fly survival following oral challenge with entomopathogen\n                    <jats:italic>Serratia marcescens<\/jats:italic>\n                    , likely due to earlier epithelial immune responses through a compromised PM. Similar phenotypes were observed when flies were fed anti-PGRP-LA antibodies, supporting a structural role for PGRP-LA. In addition, soluble variant surface glycoproteins (sVSGs) from trypanosomes and knockdown of\n                    <jats:italic>microRNA-275<\/jats:italic>\n                    (miR-275\n                    <jats:italic>)<\/jats:italic>\n                    , also decreased\n                    <jats:italic>pgrp-la<\/jats:italic>\n                    expression, suggesting that PGRP-LA is part of a broader regulatory network, including the miR-275\/Wingless signaling. Collectively, our results identify PGRP-LA as novel regulator of PM biogenesis and vector competence in tsetse, expanding the functional repertoire of PGRPs in insect gut barrier maintenance beyond canonical immune signaling pathways.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013520","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T17:47:20Z","timestamp":1777916840000},"page":"e1013520","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["PGRP-LA regulates peritrophic matrix synthesis and influences trypanosome infection outcomes in tsetse flies"],"prefix":"10.1371","volume":"22","author":[{"given":"Aur\u00e9lien","family":"Vigneron","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian L.","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuebiao","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingwen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erick","family":"Awuoche","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Orfano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emre","family":"Aksoy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9941-143X","authenticated-orcid":true,"given":"Serap","family":"Aksoy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"ppat.1013520.ref001","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/1756-3305-4-37","article-title":"Prevention and control of malaria and sleeping sickness in Africa: Where are we and where are we going?","volume":"4","author":"V Corbel","year":"2011","journal-title":"Parasit Vectors"},{"issue":"4","key":"ppat.1013520.ref002","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1086\/656276","article-title":"Critical interplay between parasite differentiation, host immunity, and antigenic variation in trypanosome infections","volume":"176","author":"E Gjini","year":"2010","journal-title":"Am Nat"},{"key":"ppat.1013520.ref003","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.cois.2014.07.003","article-title":"Trypanosome transmission dynamics in tsetse","volume":"3","author":"S Aksoy","year":"2014","journal-title":"Curr Opin Insect Sci"},{"key":"ppat.1013520.ref004","doi-asserted-by":"crossref","first-page":"53","DOI":"10.3389\/fcimb.2013.00053","article-title":"Through the dark continent: African trypanosome development in the tsetse fly","volume":"3","author":"B Rotureau","year":"2013","journal-title":"Front Cell Infect Microbiol"},{"key":"ppat.1013520.ref005","doi-asserted-by":"crossref","first-page":"103919","DOI":"10.1016\/j.jinsphys.2019.103919","article-title":"Tsetse peritrophic matrix influences for trypanosome transmission","volume":"118","author":"S Aksoy","year":"2019","journal-title":"J Insect Physiol"},{"key":"ppat.1013520.ref006","doi-asserted-by":"crossref","first-page":"103894","DOI":"10.1016\/j.jinsphys.2019.103894","article-title":"Role of the peritrophic matrix in insect-pathogen interactions","volume":"117","author":"MA Erlandson","year":"2019","journal-title":"J Insect Physiol"},{"issue":"7","key":"ppat.1013520.ref007","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/s41564-020-0707-z","article-title":"Trypanosoma brucei colonizes the tsetse gut via an immature peritrophic matrix in the proventriculus","volume":"5","author":"C Rose","year":"2020","journal-title":"Nat 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Scott","year":"2014","journal-title":"Genome Biology"},{"key":"ppat.1013520.ref020","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1146\/annurev-ento-010814-020834","article-title":"Adenotrophic viviparity in tsetse flies: Potential for population control and as an insect model for lactation","volume":"60","author":"JB Benoit","year":"2015","journal-title":"Annu Rev Entomol"},{"issue":"22","key":"ppat.1013520.ref021","doi-asserted-by":"crossref","first-page":"12648","DOI":"10.1073\/pnas.221363798","article-title":"Tsetse immune responses and trypanosome transmission: Implications for the development of tsetse-based strategies to reduce trypanosomiasis","volume":"98","author":"Z Hao","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"29","key":"ppat.1013520.ref022","doi-asserted-by":"crossref","first-page":"12133","DOI":"10.1073\/pnas.0901226106","article-title":"Interactions between mutualist Wigglesworthia and tsetse peptidoglycan recognition protein (PGRP-LB) influence trypanosome transmission","volume":"106","author":"J Wang","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"ppat.1013520.ref023","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1111\/j.1365-2958.2006.05180.x","article-title":"Innate immune responses regulate trypanosome parasite infection of the tsetse fly Glossina morsitans morsitans","volume":"60","author":"C Hu","year":"2006","journal-title":"Mol Microbiol"},{"issue":"26","key":"ppat.1013520.ref024","doi-asserted-by":"crossref","first-page":"10552","DOI":"10.1073\/pnas.1116431109","article-title":"PGRP-LB is a maternally transmitted immune milk protein that influences symbiosis and parasitism in tsetse\u2019s offspring","volume":"109","author":"J Wang","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"ppat.1013520.ref025","article-title":"Infections with immunogenic trypanosomes reduce tsetse reproductive fitness: Potential impact of different parasite strains on vector population structure","volume":"2","author":"C Hu","year":"2008","journal-title":"PLoS Negl Trop Dis"},{"issue":"7","key":"ppat.1013520.ref026","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0069742","article-title":"Functional analysis of PGRP-LA in Drosophila immunity","volume":"8","author":"M Gendrin","year":"2013","journal-title":"PLoS One"},{"issue":"1","key":"ppat.1013520.ref027","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s13071-019-3876-y","article-title":"Gut microbiota is essential in PGRP-LA regulated immune protection against Plasmodium berghei infection","volume":"13","author":"L Gao","year":"2020","journal-title":"Parasit Vectors"},{"issue":"1","key":"ppat.1013520.ref028","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1186\/s12864-016-3283-0","article-title":"Tsetse fly tolerance to T. brucei infection: Transcriptome analysis of trypanosome-associated changes in the tsetse fly salivary gland","volume":"17","author":"I Matetovici","year":"2016","journal-title":"BMC Genomics"},{"issue":"6182","key":"ppat.1013520.ref029","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1126\/science.1249656","article-title":"Genome sequence of the tsetse fly (Glossina morsitans): Vector of African trypanosomiasis","volume":"344","author":"Initiative International Glossina Genome","year":"2014","journal-title":"Science"},{"issue":"7","key":"ppat.1013520.ref030","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/ni1356","article-title":"PGRP-LC and PGRP-LE have essential yet distinct functions in the drosophila immune response to monomeric DAP-type peptidoglycan","volume":"7","author":"T Kaneko","year":"2006","journal-title":"Nat Immunol"},{"issue":"4","key":"ppat.1013520.ref031","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1159\/000452797","article-title":"The Peptidoglycan Recognition Proteins PGRPLA and PGRPLB Regulate Anopheles Immunity to Bacteria and Affect Infection by Plasmodium","volume":"9","author":"M Gendrin","year":"2017","journal-title":"J Innate Immun"},{"issue":"4","key":"ppat.1013520.ref032","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1006972","article-title":"A fine-tuned vector-parasite dialogue in tsetse\u2019s cardia determines peritrophic matrix integrity and trypanosome transmission success","volume":"14","author":"A Vigneron","year":"2018","journal-title":"PLoS Pathog"},{"issue":"11","key":"ppat.1013520.ref033","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/j.ibmb.2003.07.001","article-title":"Proventriculus (cardia) plays a crucial role in immunity in tsetse fly (Diptera: Glossinidiae)","volume":"33","author":"Z Hao","year":"2003","journal-title":"Insect Biochem Mol Biol"},{"issue":"6","key":"ppat.1013520.ref034","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1009475","article-title":"Paratransgenic manipulation of a tsetse microRNA alters the physiological homeostasis of the fly\u2019s midgut environment","volume":"17","author":"L Yang","year":"2021","journal-title":"PLoS Pathog"},{"issue":"4","key":"ppat.1013520.ref035","first-page":"857","article-title":"Rapid Expansion of Immune-Related Gene Families in the House Fly, Musca domestica","volume":"34","author":"TB Sackton","year":"2017","journal-title":"Mol Biol Evol"},{"issue":"3","key":"ppat.1013520.ref036","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1534\/g3.117.300493","article-title":"Uncovering Genomic Regions Associated with Trypanosoma Infections in Wild Populations of the Tsetse Fly Glossina fuscipes","volume":"8","author":"A Gloria-Soria","year":"2018","journal-title":"G3 (Bethesda)"},{"issue":"14","key":"ppat.1013520.ref037","doi-asserted-by":"crossref","first-page":"4301","DOI":"10.1128\/AEM.00079-14","article-title":"Analysis of multiple tsetse fly populations in Uganda reveals limited diversity and species-specific gut microbiota","volume":"80","author":"E Aksoy","year":"2014","journal-title":"Appl Environ Microbiol"},{"issue":"21","key":"ppat.1013520.ref038","doi-asserted-by":"crossref","first-page":"7760","DOI":"10.1128\/AEM.01858-12","article-title":"OmpA-mediated biofilm formation is essential for the commensal bacterium Sodalis glossinidius to colonize the tsetse fly gut","volume":"78","author":"MA Maltz","year":"2012","journal-title":"Appl Environ Microbiol"},{"issue":"1588","key":"ppat.1013520.ref039","first-page":"805","article-title":"Dynamics of multiple symbiont density regulation during host development: tsetse fly and its microbial flora","volume":"273","author":"RVM Rio","year":"2006","journal-title":"Proc Biol Sci"},{"issue":"3","key":"ppat.1013520.ref040","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/j.1365-2583.2008.00805.x","article-title":"Characterization of the antimicrobial peptide attacin loci from Glossina morsitans","volume":"17","author":"J Wang","year":"2008","journal-title":"Insect Mol 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Bryant","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5768","key":"ppat.1013520.ref044","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1126\/science.1123056","article-title":"Structure of tracheal cytotoxin in complex with a heterodimeric pattern-recognition receptor","volume":"311","author":"C-I Chang","year":"2006","journal-title":"Science"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1013520","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000}}],"container-title":["PLOS 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