{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T23:33:55Z","timestamp":1789515235870,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013994","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000}}],"reference-count":82,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT165854, PS173314 and PJT198006"],"award-info":[{"award-number":["PJT165854, PS173314 and PJT198006"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Respiratory infections are among the leading causes of illness and death. The lack or limited effectiveness of vaccines for many respiratory pathogens underscores the urgent need for alternative, broadly protective strategies. While adaptive immunity is commonly used in vaccine development, the therapeutic potential of activating and enhancing innate immunity remains underutilized. Innate immune\u2013focused interventions could offer rapid, pathogen-independent protection, bridging the gap until pathogen-specific responses develop. Therefore, exploring new broad-spectrum innate immune-targeting immunomodulatory agents can be an effective way to prevent and treat respiratory infections. Heat-killed\n                    <jats:italic>Caulobacter crescentus<\/jats:italic>\n                    (HKCC) is a potential innate immune modulator. We tested its preventive and therapeutic effects against key respiratory bacterial (\n                    <jats:italic>Mycobacterium avium<\/jats:italic>\n                    ,\n                    <jats:italic>Mav<\/jats:italic>\n                    ) and viral (SARS-CoV-2 and influenza) infections in animal models. Notably, intranasal or oral treatment with HKCC significantly lowered bacterial loads in mice infected with\n                    <jats:italic>Mav<\/jats:italic>\n                    , while activating mucosal innate immune responses and enhancing downstream cellular and antibody responses. Additionally, decreased viral loads and improved pathogenesis were seen in mice and hamsters infected with influenza and SARS-CoV-2, respectively. HKCC showed promising ability to induce strong, localized, and systemic immunity, making it a compelling candidate for developing as a human preventive or adjunct therapy for multiple respiratory diseases.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013994","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T18:45:39Z","timestamp":1772045139000},"page":"e1013994","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Host-directed broad-spectrum immunotherapeutic strategy for respiratory infections: Heat-killed Caulobacter crescentus (HKCC) as an innate-immune based biotherapeutic\/postbiotic"],"prefix":"10.1371","volume":"22","author":[{"given":"Shanika","family":"Werellagama","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raj 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Envisioning future strategies for vaccination against tuberculosis. 2006."},{"key":"ppat.1013994.ref064","doi-asserted-by":"crossref","unstructured":"Ishida E, Corrigan DT, Chen T, Liu Y, Kim RS, Song L, et al. Mucosal and systemic antigen-specific antibody responses correlate with protection against active tuberculosis in nonhuman primates. 2023.","DOI":"10.1016\/j.ebiom.2023.104897"},{"issue":"2","key":"ppat.1013994.ref065","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/s41577-022-00734-z","article-title":"Host-directed immunotherapy of viral and bacterial infections: past, present and future","volume":"23","author":"RS Wallis","year":"2023","journal-title":"Nat Rev Immunol"},{"issue":"9","key":"ppat.1013994.ref066","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.3390\/v12091039","article-title":"Induction of the Antiviral Immune Response and Its Circumvention by Coronaviruses","volume":"12","author":"P Liu","year":"2020","journal-title":"Viruses"},{"issue":"4","key":"ppat.1013994.ref067","doi-asserted-by":"crossref","first-page":"845","DOI":"10.3390\/pathogens3040845","article-title":"Animal models for influenza viruses: implications for universal vaccine development","volume":"3","author":"I Margine","year":"2014","journal-title":"Pathogens"},{"issue":"4","key":"ppat.1013994.ref068","article-title":"Broadly Effective ACE2 Decoy Proteins Protect Mice from Lethal SARS-CoV-2 Infection","volume":"11","author":"M Lu","year":"2023","journal-title":"Microbiol Spectr"},{"key":"ppat.1013994.ref069","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.ejpb.2021.04.003","article-title":"Oral inhalation for delivery of proteins and peptides to the lungs","volume":"163","author":"E Fr\u00f6hlich","year":"2021","journal-title":"Eur J Pharm Biopharm"},{"key":"ppat.1013994.ref070","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.coviro.2017.11.002","article-title":"Immune responses in influenza A virus and human coronavirus infections: an ongoing battle between the virus and host","volume":"28","author":"J Zheng","year":"2018","journal-title":"Curr Opin Virol"},{"issue":"1","key":"ppat.1013994.ref071","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1128\/CVI.00357-07","article-title":"Elevated frequency of gamma interferon-producing NK cells in healthy adults vaccinated against influenza virus","volume":"15","author":"BR Long","year":"2008","journal-title":"Clin Vaccine Immunol"},{"key":"ppat.1013994.ref072","doi-asserted-by":"crossref","first-page":"101008","DOI":"10.1016\/j.mam.2021.101008","article-title":"Innate lymphoid cells (ILC) in SARS-CoV-2 infection","volume":"80","author":"A Kumar","year":"2021","journal-title":"Mol Aspects Med"},{"key":"ppat.1013994.ref073","doi-asserted-by":"crossref","unstructured":"Kumar A, Kumari R, Liu T, Cao W, Davidson BA, Knight PR. Human Innate Lymphoid Cells in Influenza Infection and Vaccination. 2021.","DOI":"10.1615\/CritRevImmunol.2021040801"},{"issue":"3","key":"ppat.1013994.ref074","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1007\/s10787-022-00992-2","article-title":"COVID-19 and the role of cytokines in this disease","volume":"30","author":"A Hasanvand","year":"2022","journal-title":"Inflammopharmacology"},{"key":"ppat.1013994.ref075","doi-asserted-by":"crossref","first-page":"109428","DOI":"10.1016\/j.intimp.2022.109428","article-title":"Role of SARS-CoV-2-induced cytokine storm in multi-organ failure: Molecular pathways and potential therapeutic options","volume":"113","author":"Y Nazerian","year":"2022","journal-title":"Int Immunopharmacol"},{"issue":"6","key":"ppat.1013994.ref076","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.3390\/v13061011","article-title":"Animal Models for Influenza Research: Strengths and Weaknesses","volume":"13","author":"T-Q Nguyen","year":"2021","journal-title":"Viruses"},{"key":"ppat.1013994.ref077","article-title":"Animal models of mycobacteria infection","author":"IM Orme","year":"2001","journal-title":"Curr Protoc Immunol"},{"issue":"3","key":"ppat.1013994.ref078","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.01727-19","article-title":"Mechanistic Modeling of Mycobacterium tuberculosis Infection in Murine Models for Drug and Vaccine Efficacy Studies","volume":"64","author":"N Zhang","year":"2020","journal-title":"Antimicrob Agents Chemother"},{"key":"ppat.1013994.ref079","doi-asserted-by":"crossref","first-page":"776913","DOI":"10.3389\/fimmu.2021.776913","article-title":"Dynamics of Macrophage, T and B Cell Infiltration Within Pulmonary Granulomas Induced by Mycobacterium tuberculosis in Two Non-Human Primate Models of Aerosol Infection","volume":"12","author":"L Hunter","year":"2022","journal-title":"Front Immunol"},{"key":"ppat.1013994.ref080","author":"Thermofisher Corp"},{"key":"ppat.1013994.ref081","author":"Thermofisher Corp"},{"issue":"6","key":"ppat.1013994.ref082","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1165\/rcmb.2020-0280LE","article-title":"Standardization of Reporting Criteria for Lung Pathology in SARS-CoV-2-infected Hamsters: What Matters?","volume":"63","author":"AD Gruber","year":"2020","journal-title":"Am J Respir Cell Mol Biol"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1013994","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1013994","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T18:44:38Z","timestamp":1772477078000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1013994"}},"subtitle":[],"editor":[{"given":"Anne","family":"Jamet","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,2,25]]},"references-count":82,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2,25]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1013994","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,25]]}}}