{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T18:17:18Z","timestamp":1793729838463,"version":"4.6.1"},"reference-count":82,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Key Research and Development Program sponsored by the Ministry of Science and Technology","award":["2023YFA1801000"],"award-info":[{"award-number":["2023YFA1801000"]}]},{"name":"The Shanghai Pilot Program for Basic Research - Fudan University","award":["22TQ015"],"award-info":[{"award-number":["22TQ015"]}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2023M740700"],"award-info":[{"award-number":["2023M740700"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Postdoctoral Research Fellowship Program (Grade C) of China Postdoctoral Science Foundation","award":["GZC20230520"],"award-info":[{"award-number":["GZC20230520"]}]}],"content-domain":{"domain":["www.plosbiology.org"],"crossmark-restriction":false},"short-container-title":["PLoS Biol"],"abstract":"<jats:p>\n                    The peritrophic matrix (PM) acts as a physical barrier that influences the vector competence of mosquitoes. We have previously shown that gut microbiota promotes PM formation in\n                    <jats:italic>Anopheles stephensi<\/jats:italic>\n                    , although the underlying mechanisms remain unclear. In this study, we identify that the cell wall components of gut commensal bacteria contribute to PM formation. Oral administration of primary cell wall components from both gram-positive and gram-negative bacteria, such as diaminopimelic acid-peptidoglycan (DAP-PGN), lysine-peptidoglycan (Lys-PGN), and lipopolysaccharides (LPS), to mosquitoes, after depleting their gut microbiota with antibiotics, restores the down-regulated expression of the\n                    <jats:italic>peritrophin1<\/jats:italic>\n                    (\n                    <jats:italic>Per1<\/jats:italic>\n                    ) gene, which encodes a structural protein of the PM. Moreover, this administration rescues PM formation upon blood ingestion. PGN and LPS are well-known ligands of innate immune signaling pathways in animals. In mosquitoes, the Toll and IMD (immune deficiency) pathways are the 2 major innate immune signaling pathways. We next knocked down the expression of 2 receptors,\n                    <jats:italic>Pgrp-s1<\/jats:italic>\n                    and\n                    <jats:italic>Pgrp-lc<\/jats:italic>\n                    , as well as 2 transcription factors,\n                    <jats:italic>Rel1<\/jats:italic>\n                    and\n                    <jats:italic>Rel2<\/jats:italic>\n                    , which are involved in the Toll and IMD pathways, respectively. Double knockdown of\n                    <jats:italic>Pgrp-s1<\/jats:italic>\n                    and\n                    <jats:italic>Pgrp-lc<\/jats:italic>\n                    , or\n                    <jats:italic>Rel1<\/jats:italic>\n                    and\n                    <jats:italic>Rel2<\/jats:italic>\n                    , compromised\n                    <jats:italic>Per1<\/jats:italic>\n                    expression. Additionally, through dual-luciferase assays and supershift electrophoretic mobility shift assays (EMSAs), we identified a 15-bp binding motif (ATAGACACGAGCACC) for Rel1 and Rel2 in the\n                    <jats:italic>Per1<\/jats:italic>\n                    promoter region. To further explore the role of individual Toll and IMD pathways in the regulation of\n                    <jats:italic>Per1<\/jats:italic>\n                    expression, we specifically inhibited the activity of each pathway. While inhibition of the Toll pathway by knocking down\n                    <jats:italic>Pgrp-s1<\/jats:italic>\n                    or\n                    <jats:italic>Rel1<\/jats:italic>\n                    did not affect\n                    <jats:italic>Per1<\/jats:italic>\n                    expression, knockdown of\n                    <jats:italic>Pgrp-lc<\/jats:italic>\n                    or\n                    <jats:italic>Rel2<\/jats:italic>\n                    in the IMD pathway significantly down-regulated\n                    <jats:italic>Per1<\/jats:italic>\n                    expression. These findings suggest that the IMD pathway plays a major role in regulating\n                    <jats:italic>Per1<\/jats:italic>\n                    expression in\n                    <jats:italic>An<\/jats:italic>\n                    .\n                    <jats:italic>stephensi<\/jats:italic>\n                    . In summary, our study uncovers a novel role for bacterial cell wall components in regulating PM formation through activation of mosquito immune signaling pathways.\n                  <\/jats:p>","DOI":"10.1371\/journal.pbio.3002967","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T13:21:47Z","timestamp":1736169707000},"page":"e3002967","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":22,"title":["Cell wall components of gut commensal bacteria stimulate peritrophic matrix formation in malaria vector mosquitoes through activation of the IMD pathway"],"prefix":"10.1371","volume":"23","author":[{"given":"Xiumei","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6794-2604","authenticated-orcid":true,"given":"Jingwen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,1,6]]},"reference":[{"issue":"12","key":"pbio.3002967.ref001","first-page":"573","article-title":"Spreading the seeds of million-murdering death: metamorphoses of malaria in the mosquito","volume":"21","author":"LA Baton","year":"2005","journal-title":"Trends Parasitol"},{"issue":"7","key":"pbio.3002967.ref002","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.ibmb.2004.03.019","article-title":"Mosquito midgut barriers to malaria parasite development","volume":"34","author":"EG Abraham","year":"2004","journal-title":"Insect Biochem Mol Biol"},{"issue":"5","key":"pbio.3002967.ref003","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S1471-4922(01)01928-6","article-title":"Plasmodium invasion of mosquito cells: hawk or dove?","volume":"17","author":"RE Sinden","year":"2001","journal-title":"Trends Parasitol"},{"issue":"4","key":"pbio.3002967.ref004","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/j.1365-3024.2006.00804.x","article-title":"Mosquito midguts and malaria: cell biology, compartmentalization and immunology","volume":"28","author":"MMA Whitten","year":"2006","journal-title":"Parasite Immunol"},{"key":"pbio.3002967.ref005","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"},{"key":"pbio.3002967.ref006","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. 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