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In Australia, only two distinct rat lungworm cox1 haplotypes have been detected in clinically affected dogs, with haplotype Ac13 implicated in most cases. Using locally sourced isolates, we enquired whether the brain migrating larvae elicit different host response in its natural host. We examined brain transcriptome, faecal shedding rates, and adult worm of A. cantonensis isolates representing two distinct cox1 haplotypes, SYD.1 and Ac13 (represented by isolate SYD.2), in experimentally infected Wistar rats. For SYD.1-infected rats, only one differentially expressed gene (DEG) was upregulated in the compared to controls. In contrast, the transcriptome of SYD.2-infected rats included 100 DEGs, with enrichment of functional terms related to immune response, neuroactivity, and signalling. Faecal shedding did not differ between SYD.1- and SYD.2-infected rats, but adult worm burdens were higher in the SYD.1 group. The increased immune response in SYD.2-infected rats provides evidence that there is strain specific virulence that is pronounced in its natural host. This study provides initial parasite-specific evidence explaining why clinically affected dogs are more frequently presented with A. cantonensis haplotype Ac13.<\/jats:p>","DOI":"10.1093\/femspd\/ftaf003","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T03:47:36Z","timestamp":1740023256000},"source":"Crossref","is-referenced-by-count":1,"title":["Isolate-specific rat brain transcriptional responses to rat lungworm (<i>Angiostrongylus cantonensis<\/i>)"],"prefix":"10.1093","volume":"83","author":[{"given":"Phoebe","family":"Rivory","sequence":"first","affiliation":[{"name":"Sydney School of Veterinary Science, Faculty of Science, The University of Sydney , NSW 2006 ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rogan","family":"Lee","sequence":"additional","affiliation":[{"name":"NSW Health Pathology, Centre for Infectious Diseases and Microbiology Lab Services, Level 3 ICPMR, Westmead Hospital , Westmead, NSW 2145 ,","place":["Australia"]},{"name":"School of Biomedical Sciences, Faculty of Medicine and Health, The University of Sydney , NSW 2006 ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1459-9117","authenticated-orcid":false,"given":"Jan","family":"\u0160lapeta","sequence":"additional","affiliation":[{"name":"Sydney School of Veterinary Science, Faculty of Science, The University of Sydney , NSW 2006 ,","place":["Australia"]},{"name":"Sydney Infectious Diseases Institute, The University of Sydney , NSW 2006 ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,2,19]]},"reference":[{"key":"2025031114524829000_bib1","first-page":"1105","article-title":"Degradation of human matrix metalloprotease-9 by secretory metalloproteases of Angiostrongylus cantonensis infective 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