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Cathelicidins are host defense peptides known for their antimicrobial and immunomodulatory functions, but their role in N. caninum infections remains elusive. Using bone marrow-derived macrophages (BMDMs) isolated from mice expressing (wild-type, Camp+\/+) and lacking (Camp\u2212\/\u2212) cathelicidins, we investigated the role of endogenous cathelicidin in infections with N. caninum. We show that Camp\u2212\/\u2212 macrophages primed with lipopolysaccharide (LPS) had an increased number of intracellular N. caninum tachyzoites, and these macrophages released higher amounts of IL-1\u03b2 and lactate dehydrogenase (LDH), a marker of cytotoxicity. These findings indicate that cathelicidins contribute to intracellular N. caninum control and inflammation by limiting the activation of the inflammasome, particularly under LPS-induced conditions. This insight reveals the immunomodulatory role of cathelicidins in controlling N. caninum-associated pathologies.<\/jats:p>","DOI":"10.3390\/pathogens14070663","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T08:58:23Z","timestamp":1751878703000},"page":"663","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cathelicidins Limit Intracellular Neospora caninum-Infection in Macrophages"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1895-5695","authenticated-orcid":false,"given":"Franco","family":"Fiorani","sequence":"first","affiliation":[{"name":"Faculty of Agricultural Sciences, National University of Mar Del Plata, Balcarce B7620, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyoshi","family":"Lahiri","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Puentes","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter John","family":"Bradley","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6735-3810","authenticated-orcid":false,"given":"Dadin Prando","family":"Moore","sequence":"additional","affiliation":[{"name":"Faculty of Agricultural Sciences, National University of Mar Del Plata, Balcarce B7620, Argentina"},{"name":"Institute of Innovation for Agricultural Production and Sustainable Development (IPADS), Balcarce B7620, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5450-7673","authenticated-orcid":false,"given":"Eduardo Ruben","family":"Cobo","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.cvfa.2019.11.004","article-title":"Neosporosis, Toxoplasmosis, and Sarcocystosis in Ruminants: An Update","volume":"36","author":"Lindsay","year":"2020","journal-title":"Vet. 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