{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:39:42Z","timestamp":1786700382872,"version":"build-2736575974"},"reference-count":41,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"various revenue streams of the corresponding author\u2019s laboratory at the University of Georgia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>The host cellular mechanisms determining whether Dirofilaria immitis (canine heartworm) larvae establish infection remain poorly understood. The Mongolian gerbil (Meriones unguiculatus), a naturally nonpermissive host, mounts a rapid macrophage-dominated peritoneal cellular response to intraperitoneal (IP) larval challenge. To test whether macrophages mediate larval clearance, peritoneal macrophages were selectively depleted with IP clodronate liposomes (100 \u00b5L\/10 g body weight; days \u22124 and \u22121 relative to infection) before challenge with approximately 40 D. immitis third-stage larvae (L3). A rat anti-mouse anti-F4\/80 antibody was validated as a cross-reactive macrophage marker in jird peritoneal exudate cells (PECs) by standard and imaging flow cytometry, and depletion efficacy was confirmed prior to infection. Significantly more L3 were recovered from macrophage-depleted jirds (mean = 17.7%; SEM = 6.0%) than from PBS liposome controls (mean = 3.8%; SEM = 1.9%) at 1-day post-infection (p &lt; 0.03). Cytology and flow cytometry confirmed near-complete macrophage depletion, and a significant compensatory neutrophilia was observed in depleted animals (64.5% \u00b1 5.7% vs. 19.6% \u00b1 5.1% in controls; p &lt; 0.0001). These findings establish peritoneal macrophages as the primary innate cellular mediators of D. immitis L3 clearance in a nonpermissive host, providing a validated in vivo framework for mechanistic dissection of filarial host specificity.<\/jats:p>","DOI":"10.3390\/pathogens15080851","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:04:01Z","timestamp":1786698241000},"page":"851","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Role of Macrophages in the Immune Response to Peritoneal Infection with Dirofilaria immitis Larvae in the Mongolian Gerbil (Meriones unguiculatus)"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1096-1510","authenticated-orcid":false,"given":"Elyssa","family":"Campbell","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Pope","sequence":"additional","affiliation":[{"name":"Division of Animal Resources, Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katelin","family":"Greenway","sequence":"additional","affiliation":[{"name":"Veterinary Medicine Research and Development, Zoetis, Kalamazoo, MI 49007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget","family":"Garner","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6473-3743","authenticated-orcid":false,"given":"Andrew","family":"Moorhead","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","unstructured":"Companion Animal Parasite Council (2026, February 06). 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