Comparative development of human filariae Loa loa, Onchocerca volvulus and Mansonella perstans in immunocompromised mouse strains

• Published in: Frontiers in Tropical Diseases
• Main Authors: Valerine C. Chunda, Fanny Fri Fombad, Chi Anizette Kien, Rene Ebai, Frederick Esofi, Anna Ning Ntuh, Emmanuel Ouam, Narcisse Victor Tchamatchoua Gandjui, Relindis Ekanya, Franck Nietcho, Lucy Cho Nchang, Chefor Magha, Abdel Jelil Njouendou, Peter Enyong, Achim Hoerauf, Samuel Wanji, Manuel Ritter
• Format: Article in Journal/Newspaper
• Language: English
• Published: Frontiers Media S.A. 2024
• Subjects: Mansonella perstans; Loa loa; Onchocerca volvulus; murine models of human filariasis; immunocompromised mice; Arctic medicine. Tropical medicine; RC955-962; Arctic
• Online Access: https://doi.org/10.3389/fitd.2024.1293632; https://doaj.org/article/d2066627f88a44eca8ac60bfc4366a77

IntroductionMouse models of human filarial infections are not only urgently needed to investigate the biology of the nematodes and their modulation of the host’s immunity, but will also provide a platform to screen and test novel anti-filarial drugs. Recently, murine Loa loa infection models have been stablished using immunocompromised mouse strains, whereas murine Mansonella perstans infections have not been implemented until now.MethodsTherefore, we aim to establish experimental M. perstans infections using the immunocompromised mouse strains RAG2IL-2Rγ-/- (lack B, T and natural killer cells), IL-4Rα/IL-5-/- (impaired IL-4/5 signalling and eosinophil activation) and NOD.Cg-PrkdcscidIl2rgtm1Wj l/SzJ (NOD scid gamma, NSG) BALB/c mice (lack mature lymphocytes) through subcutaneous (s.c.) or intraperitoneal (i.p.) inoculation of infective stage 3 larvae (L3) isolated from engorged vectors.ResultsIn total, 145 immunocompromised mice have been inoculated with 3,250 M. perstans, 3,337 O. volvulus, and 2,720 Loa loa L3 to comparatively analyse which immunocompromised mouse strain is susceptible to human filarial infections. Whereas, no M. perstans and O. volvulus L3 could be recovered upon 2-63 days post-inoculation, a 62-66% Loa loa L3 recovery rate could be achieved in the different mouse strains. Gender of mice, type of inoculation (s.c. or i.p.) or time point of analysis (2-63 days post inoculation) did not interfere with the success of L3 recovery. In addition, administration of the immune suppressants hydrocortisone, prednisolone and cyclophosphamide did not restore M. perstans L3 recovery rates.DiscussionThese findings show that RAG2IL-2Rg-/-BALB/c and C57BL/6, IL-4Rα/IL-5-/- BALB/c and NSG mice were not susceptible to M. perstans and O. volvulus L3 inoculation using the applied methods, whereas Loa loa infection could be maintained. Further studies should investigate if humanized immunocompromised mice might be susceptible to M. perstans. and O. volvulus.