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Mouse models of Loa loa

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Pionnier, Nicolas. P ORCID: https://orcid.org/0000-0002-2379-4945, Sjoberg, Hanna, Chunda, Valerine C, Fombad, Fanny F, Chounna, Patrick W, Njouendou, Abdel J, Metuge, Haelly M, Ndzeshang, Bertrand, Gandjui, Narcisse, Akumtoh, Desmond N, Tayong, Dizzle B, Taylor, Mark J ORCID: https://orcid.org/0000-0003-3396-9275, Wanji, Samual and Turner, Joseph D ORCID: https://orcid.org/0000-0002-2185-5476 (2019) 'Mouse models of Loa loa'. Nature Communications, Vol 10, Issue 1429.

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Abstract

Elimination of the helminth disease, river blindness, remains challenging due to ivermectin treatment-associated adverse reactions in loiasis co-infected patients. Here, we address a deficit in preclinical research tools for filarial translational research by developing Loa loa mouse infection models. We demonstrate that adult Loa loa worms in subcutaneous tissues, circulating microfilariae (mf) and presence of filarial biomarkers in sera occur following experimental infections of lymphopenic mice deficient in interleukin (IL)-2/7 gamma-chain signaling. A microfilaraemic infection model is also achievable, utilizing immune-competent or -deficient mice infused with purified Loa mf. Ivermectin but not benzimidazole treatments induce rapid decline (>90%) in parasitaemias in microfilaraemic mice. We identify up-regulation of inflammatory markers associated with allergic type-2 immune responses and eosinophilia post-ivermectin treatment. Thus, we provide validation of murine research models to identify loiasis biomarkers, to counter-screen candidate river blindness cures and to interrogate the inflammatory etiology of loiasis ivermectin-associated adverse reactions.

Item Type: Article
Subjects: QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 253 Anthelmintics
QX Parasitology > Helminths. Annelida > QX 200 Helminths
QX Parasitology > Helminths. Annelida > QX 301 Filarioidea
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 880 Filariasis and related conditions (General)
WW Ophthalmology > Diseases. Color Perception > WW 160 Eye infections. Hypersensitivity diseases (General or not elsewhere classified)
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI): https://doi.org/10.1038/s41467-019-09442-0
Depositing User: Stacy Murtagh
Date Deposited: 01 Apr 2019 14:13
Last Modified: 16 Sep 2019 09:02
URI: https://archive.lstmed.ac.uk/id/eprint/10525

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