Mouse models of Loa loa

Nicolas P. Pionnier, Hanna Sjoberg, Valerine C. Chunda, Fanny F. Fombad, Patrick W. Chounna, Abdel J. Njouendou, Haelly M. Metuge, Bertrand L. Ndzeshang, Narcisse V. Gandjui, Desmond N. Akumtoh, Dizzle B. Tayong, Mark J. Taylor, Samuel Wanji and Joseph D. Turner ()
Additional contact information
Nicolas P. Pionnier: Liverpool School of Tropical Medicine, Pembroke Place
Hanna Sjoberg: Liverpool School of Tropical Medicine, Pembroke Place
Valerine C. Chunda: Research Foundation in Tropical Diseases and the Environment
Fanny F. Fombad: Research Foundation in Tropical Diseases and the Environment
Patrick W. Chounna: Research Foundation in Tropical Diseases and the Environment
Abdel J. Njouendou: Research Foundation in Tropical Diseases and the Environment
Haelly M. Metuge: Research Foundation in Tropical Diseases and the Environment
Bertrand L. Ndzeshang: Research Foundation in Tropical Diseases and the Environment
Narcisse V. Gandjui: Research Foundation in Tropical Diseases and the Environment
Desmond N. Akumtoh: Research Foundation in Tropical Diseases and the Environment
Dizzle B. Tayong: Research Foundation in Tropical Diseases and the Environment
Mark J. Taylor: Liverpool School of Tropical Medicine, Pembroke Place
Samuel Wanji: Research Foundation in Tropical Diseases and the Environment
Joseph D. Turner: Liverpool School of Tropical Medicine, Pembroke Place

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-09442-0

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