{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T02:51:30Z","timestamp":1768013490089,"version":"3.49.0"},"reference-count":104,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T00:00:00Z","timestamp":1693785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"U. S. National Institutes of Health","doi-asserted-by":"publisher","award":["TW 010500"],"award-info":[{"award-number":["TW 010500"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"U. S. National Institutes of Health","doi-asserted-by":"publisher","award":["AI 139267"],"award-info":[{"award-number":["AI 139267"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"U. S. National Institutes of Health","doi-asserted-by":"publisher","award":["AI 171971"],"award-info":[{"award-number":["AI 171971"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Canine leishmaniosis (CanL) is a zoonotic disease caused by protozoan Leishmania infantum. Dogs with CanL are often coinfected with tick-borne bacterial pathogens, including Borrelia burgdorferi in the United States. These coinfections have been causally associated with hastened disease progression and mortality. However, the specific cellular mechanisms of how coinfections affect microbicidal responses against L. infantum are unknown. We hypothesized that B. burgdorferi coinfection impacts host macrophage effector functions, prompting L. infantum intracellular survival. In vitro experiments demonstrated that exposure to B. burgdorferi spirochetes significantly increased L. infantum parasite burden and pro-inflammatory responses in DH82 canine macrophage cells. Induction of cell death and generation of mitochondrial ROS were significantly decreased in coinfected DH82 cells compared to uninfected and L. infantum-infected cells. Ex vivo stimulation of PBMCs from L. infantum-seronegative and -seropositive subclinical dogs with spirochetes and\/or total Leishmania antigens promoted limited induction of IFN\u03b3. Coexposure significantly induced expression of pro-inflammatory cytokines and chemokines associated with Th17 differentiation and neutrophilic and monocytic recruitment in PBMCs from L. infantum-seropositive dogs. Excessive pro-inflammatory responses have previously been shown to cause CanL pathology. This work supports effective tick prevention and risk management of coinfections as critical strategies to prevent and control L. infantum progression in dogs.<\/jats:p>","DOI":"10.3390\/pathogens12091128","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T10:14:11Z","timestamp":1693822451000},"page":"1128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Modulation of Macrophage Redox and Apoptotic Processes to Leishmania infantum during Coinfection with the Tick-Borne Bacteria Borrelia burgdorferi"],"prefix":"10.3390","volume":"12","author":[{"given":"Danielle","family":"Pess\u00f4a-Pereira","sequence":"first","affiliation":[{"name":"Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Center for Emerging Infectious Diseases, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3489-0270","authenticated-orcid":false,"given":"Breanna M.","family":"Scorza","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Center for Emerging Infectious Diseases, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen I.","family":"Cyndari","sequence":"additional","affiliation":[{"name":"Center for Emerging Infectious Diseases, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Department of Emergency Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin A.","family":"Beasley","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Center for Emerging Infectious Diseases, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine A.","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Center for Emerging Infectious Diseases, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/S0140-6736(18)31204-2","article-title":"Leishmaniasis","volume":"392","author":"Burza","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100041","DOI":"10.1016\/j.cytox.2020.100041","article-title":"Macrophages as host, effector and immunoregulatory cells in leishmaniasis: Impact of tissue micro-environment and metabolism","volume":"2","author":"Bogdan","year":"2020","journal-title":"Cytokine X"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"251","DOI":"10.3389\/fimmu.2012.00251","article-title":"Immunobiology of visceral leishmaniasis","volume":"3","author":"Kumar","year":"2012","journal-title":"Front. 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