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Typhimurium. Here we show that a Salmonella phage, F118P13, with non-productive infection and a lytic phage, PLL1, combined to inhibit pandrug-resistant S. Typhimurium growth and significantly limited resistance to phages in vitro. Further, intraperitoneal injection with this unique phage combination completely protected mice from Salmonella-induced death and inhibited bacterial proliferation rapidly in various organs. Furthermore, the phage combination treatment significantly attenuated the inflammatory response, restored the generation of CD4+ T cells repressed by Salmonella, and allowed macrophages and granulocytes to participate in immunophage synergy to promote bacterial clearance. Crucially, the non-productive phage F118P13 is less likely to be cleared by the immune system in vivo, thus providing an alternative to phage cocktail against bacterial infections.<\/jats:p>","DOI":"10.3390\/ijms232112830","type":"journal-article","created":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T11:53:55Z","timestamp":1666612435000},"page":"12830","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Combination of Virulent and Non-Productive Phages Synergizes the Immune System against Salmonella Typhimurium Systemic Infection"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4967-0315","authenticated-orcid":false,"given":"Lu","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Tai\u2019an 271018, China"},{"name":"Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Tai\u2019an 271018, China"},{"name":"Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ketong","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Tai\u2019an 271018, China"},{"name":"Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Tai\u2019an 271018, China"},{"name":"Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjian","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Tai\u2019an 271018, China"},{"name":"Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Tai\u2019an 271018, China"},{"name":"Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4074-4023","authenticated-orcid":false,"given":"Guijuan","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Tai\u2019an 271018, China"},{"name":"Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0059-6759","authenticated-orcid":false,"given":"Shuhong","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Tai\u2019an 271018, China"},{"name":"Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18379","DOI":"10.1039\/C5NR05226B","article-title":"Biomimetic sensor design","volume":"7","author":"Lee","year":"2015","journal-title":"Nanoscale"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1080\/21553769.2015.1051243","article-title":"Salmonella: A review on pathogenesis, epidemiology and antibiotic resistance","volume":"8","author":"Eng","year":"2015","journal-title":"Front. 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