Comparative development of human filariae and in immunocompromised mouse strains.

INTRODUCTION: Mouse 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 infection models have been stablished using immunocompromised mouse strains, whereas murine infections have not been implemented until now.

METHODS: Therefore, we aim to establish experimental 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-PrkdcIl2rg 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.

RESULTS: In total, 145 immunocompromised mice have been inoculated with 3,250 , 3,337 , and 2,720 L3 to comparatively analyse which immunocompromised mouse strain is susceptible to human filarial infections. Whereas, no and L3 could be recovered upon 2-63 days post-inoculation, a 62-66% 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 L3 recovery rates.

DISCUSSION: These findings show that RAG2IL-2RgBALB/c and C57BL/6, IL-4Rα/IL-5 BALB/c and NSG mice were not susceptible to and L3 inoculation using the applied methods, whereas infection could be maintained. Further studies should investigate if humanized immunocompromised mice might be susceptible to . and .

PMID: 38655273