{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T23:33:57Z","timestamp":1789515237696,"version":"build-2803163510"},"reference-count":74,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T00:00:00Z","timestamp":1675900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Canadian Institutes of Health Research","award":["PJT165854"],"award-info":[{"award-number":["PJT165854"]}]},{"name":"Canadian Institutes of Health Research","award":["PS173314"],"award-info":[{"award-number":["PS173314"]}]},{"name":"Canadian Institutes of Health Research","award":["MOP49415"],"award-info":[{"award-number":["MOP49415"]}]},{"name":"CIHR graduate studentship award","award":["PJT165854"],"award-info":[{"award-number":["PJT165854"]}]},{"name":"CIHR graduate studentship award","award":["PS173314"],"award-info":[{"award-number":["PS173314"]}]},{"name":"CIHR graduate studentship award","award":["MOP49415"],"award-info":[{"award-number":["MOP49415"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is a serious and devastating infectious disease worldwide. Approximately a quarter of the world population harbors latent Mtb infection without pathological consequences. Exposure of immunocompetent healthy individuals with Mtb does not result in active disease in more than 90% individuals, suggesting a defining role of host immunity to prevent and\/or clear early infection. However, innate immune stimulation strategies have been relatively underexplored for the treatment of tuberculosis. In this study, we used cell culture and mouse models to examine the role of a heat-killed form of a non-pathogenic microbe, Caulobacter crescentus (HKCC), in inducing innate immunity and limiting Mtb infection. We also examined the added benefits of a distinct chemo-immunotherapeutic strategy that incorporates concurrent treatments with low doses of a first-line drug isoniazid and HKCC. This therapeutic approach resulted in highly significant reductions in disseminated Mtb in the lungs, liver, and spleen of mice compared to either agent alone. Our studies demonstrate the potential of a novel innate immunotherapeutic strategy with or without antimycobacterial drugs in controlling Mtb infection in mice and open new avenues for the treatment of tuberculosis in humans.<\/jats:p>","DOI":"10.3390\/cells12040560","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T03:52:49Z","timestamp":1676001169000},"page":"560","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Harnessing Innate Immunity to Treat Mycobacterium tuberculosis Infections: Heat-Killed Caulobacter crescentus as a Novel Biotherapeutic"],"prefix":"10.3390","volume":"12","author":[{"given":"Nancy","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 1C9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satish","family":"Vedi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 1C9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saurabh","family":"Garg","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 1C9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Loo","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 2S2, Canada"},{"name":"Mitacs, University of British Columbia, Vancouver, BC V6T 1Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 2S2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis Y.","family":"Kunimoto","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 2R7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 1C9, Canada"},{"name":"ImMed Biotechnologies, Edmonton, AB T6R 2E8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1957-6371","authenticated-orcid":false,"given":"Babita","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine and Dentistry, College of Health Sciences, University of Alberta, Edmonton, AB T6G 2S2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,9]]},"reference":[{"key":"ref_1","unstructured":"WHO (2022, October 06). 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