Host environment shapes filarial parasite fitness and Wolbachia endosymbionts dynamics

Filarial nematodes, responsible for diseases like lymphatic filariasis and onchocerciasis, depend on symbiotic Wolbachia bacteria for reproduction and development. Using the Litomosoides sigmodontis rodent model, we investigated how host type-2 immunity influences Wolbachia dynamics and parasite development. Wild-type and type-2 immune-deficient ( Il4rα ⁻/⁻ Il5 ⁻/⁻ ) BALB/c mice were infected with L. sigmodontis , and the distribution and abundance of Wolbachia were analyzed at different developmental stages using quantitative PCR and fluorescence in situ hybridization. Our results show that type-2 immune environments selectively reduce germline Wolbachia in female filariae from wild-type mice, a change associated with disrupted oogenesis, embryogenesis, and microfilarial production, while somatic Wolbachia remain unaffected. Antibiotic treatments achieving systemic Wolbachia clearance result in similar reproductive impairments. Notably, Wolbachia -free microfilariae are observed shortly after Wolbachia depletion, suggesting that early-stage embryogenesis can proceed temporarily before progressive germline dysfunction ensues. Wolbachia -free microfilariae develop into infective larvae in the vector, but stall beyond the L4 stage in vertebrate hosts, showing arrested growth and reproductive organ maturation defects in both male and female larvae. These findings highlight the variable dependency on Wolbachia across life stages and provide insights into host-parasite-endosymbiont interactions shaped by environmental pressures.