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Thus, we investigated the role of this insecticide in modulating humoral responses, focusing on peptidoglycan recognition proteins (PGRPs) as key mediators. PGRPs are important pattern recognition receptors that activate insect innate immunity against microbes. Our findings revealed that chlorantraniliprole inhibited humoral immunity in larvae, with the expression of SfPGRP-S5 being significantly affected. Functional studies revealed that SfPGRP-S5 knockdown under chlorantraniliprole exposure decreased larval survival following bacterial infection and downregulated antimicrobial peptide (AMP) genes, while recombinant SfPGRP-S5 activated AMP and prophenoloxidase (PPO) expression. Additionally, the transgenic Drosophila bioassay indicated that SfPGRP-S5 overexpression enhanced chlorantraniliprole tolerance and reduced bacterial susceptibility. In summary, SfPGRP-S5 plays a critical role in mediating chlorantraniliprole-induced suppression of humoral immunity in S. frugiperda larvae. This study reveals the differential immune regulation by insecticides and provides new insights for understanding their sublethal effects.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c08585","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:01:52Z","timestamp":1790848912000},"page":"31478-31490","source":"Crossref","is-referenced-by-count":0,"title":["Chlorantraniliprole\nSuppresses the Humoral Immunity\nin\n                    <i>Spodoptera frugiperda<\/i>\n                    Larvae by\nDownregulating Peptidoglycan Recognition Protein Gene\n                    <i>SfPGRP-S5<\/i>"],"prefix":"10.1021","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1411-7889","authenticated-orcid":true,"given":"Qingyan","family":"Liu","sequence":"first","affiliation":[{"name":"Sichuan Agricultural University , , ,","place":["Chengdu, China, 611130"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqi","family":"Xie","sequence":"additional","affiliation":[{"name":"Sichuan Agricultural University , , ,","place":["Chengdu, China, 611130"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Liu","sequence":"additional","affiliation":[{"name":"Sichuan Agricultural University , , ,","place":["Chengdu, China, 611130"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhua","family":"Liu","sequence":"additional","affiliation":[{"name":"Sichuan Agricultural University , , ,","place":["Chengdu, China, 611130"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyue","family":"Deng","sequence":"additional","affiliation":[{"name":"Sichuan Agricultural University , , ,","place":["Chengdu, China, 611130"]},{"name":"Emeishan Agricultural and Rural Bureau , ,","place":["Emeishan, China, 614200"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Li","sequence":"additional","affiliation":[{"name":"Sichuan Agricultural University , , ,","place":["Chengdu, China, 611130"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanli","family":"Yue","sequence":"additional","affiliation":[{"name":"Sichuan Agricultural University , , ,","place":["Chengdu, China, 611130"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4792-852X","authenticated-orcid":true,"given":"Huabao","family":"Chen","sequence":"additional","affiliation":[{"name":"Sichuan Agricultural University , , ,","place":["Chengdu, China, 611130"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qunfang","family":"Yang","sequence":"additional","affiliation":[{"name":"Sichuan Agricultural University , , ,","place":["Chengdu, China, 611130"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxian","family":"Jiang","sequence":"additional","affiliation":[{"name":"Sichuan Agricultural University , , ,","place":["Chengdu, China, 611130"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"2026101408095661600_cit1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/s0065-2806(05)32001-7","article-title":"Insect immunity:\nAn Evolutionary Ecology Perspective","volume-title":"Advances\nin Insect Physiology","author":"Siva-Jothy","year":"2005"},{"issue":"10","key":"2026101408095661600_cit2","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1016\/S0965-1748(02)00092-9","article-title":"Insect hemocytes\nand their role in immunity","volume":"32","author":"Strand","year":"2002","journal-title":"Insect Biochem.\nMol. 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