Fercoq Frédéric, Cormerais Clément, Remion Estelle, Gal Joséphine, Plisson Julien, Fall Arame, Alonso Joy, Lhermitte-Vallarino Nathaly, Hübner Marc P, Kohl Linda, Landmann Frédéric, Martin Coralie
Unité Molécules de Communication et Adaptation des Micro-organismes (MCAM, UMR 7245), Muséum National d'Histoire Naturelle, CNRS, Paris, France.
Centre de Recherche en Biologie Cellulaire de Montpellier (CRBM), Université de Montpellier, CNRS, Montpellier, France.
PLoS Pathog. 2025 Jul 11;21(7):e1013301. doi: 10.1371/journal.ppat.1013301. eCollection 2025 Jul.
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.
丝虫线虫可引发淋巴丝虫病和盘尾丝虫病等疾病，其繁殖和发育依赖共生的沃尔巴克氏体细菌。我们利用刚毛囊丝虫（Litomosoides sigmodontis）啮齿动物模型，研究了宿主2型免疫如何影响沃尔巴克氏体动态和寄生虫发育。将野生型和2型免疫缺陷（Il4rα⁻/⁻Il5⁻/⁻）的BALB/c小鼠感染刚毛囊丝虫，使用定量PCR和荧光原位杂交技术分析不同发育阶段沃尔巴克氏体的分布和丰度。我们的结果表明，2型免疫环境选择性地减少了野生型小鼠雌性丝虫种系中的沃尔巴克氏体，这一变化与卵子发生、胚胎发生和微丝蚴产生的破坏有关，而体细胞中的沃尔巴克氏体则不受影响。实现全身沃尔巴克氏体清除的抗生素治疗会导致类似的生殖障碍。值得注意的是，在沃尔巴克氏体耗竭后不久就观察到无沃尔巴克氏体的微丝蚴，这表明在渐进性种系功能障碍出现之前，早期胚胎发生可以暂时进行。无沃尔巴克氏体的微丝蚴在媒介中发育成感染性幼虫，但在脊椎动物宿主中停滞在L4阶段之后，在雄性和雌性幼虫中均表现出生长停滞和生殖器官成熟缺陷。这些发现突出了丝虫在不同生命阶段对沃尔巴克氏体的可变依赖性，并为环境压力塑造的宿主-寄生虫-内共生体相互作用提供了见解。
