Recall immunity limits Litomosoides sigmodontis growth without preventing reinfection

Background Protective immunity against reinfection with filarial nematodes remains poorly understood. We therefore investigated whether naturally acquired immunity following spontaneous parasite clearance modifies the outcome of reinfection using the permissive murine filarial model Litomosoides sigmodontis . Methods Wildtype BALB/c mice were reinfected following natural clearance of a primary L. sigmodontis infection and compared with mice during patent primary infection and after parasite clearance. Parasitological parameters, local immune cell responses, lung pathology, and systemic cytokine levels were assessed. Results Adult worms were detected in only 3 of 6 reinfected mice, indicating substantial inter-individual variation in parasite establishment. Among mice with detectable adult worms, reinfection resulted in significantly shorter adult worms, while microfilaremia, embryogenesis, and Wolbachia density were not significantly altered, indicating restricted parasite development at the time point examined without detectable effects on parasite reproductive capacity or Wolbachia density. Reinfected mice further exhibited significantly increased neutrophil accumulation and overall immune cell infiltration into the thoracic cavity, accompanied by modestly increased lung inflammation and elevated systemic levels of IFN-γ, IL-6, IL-10, IL-22, and GM-CSF. Conclusion Naturally acquired immunity following primary L. sigmodontis infection does not confer sterilising protection against reinfection, but is associated with substantial heterogeneity in parasite establishment and restricted parasite development among mice with detectable adult worms together with local and systemic recall immune responses that selectively restrict parasite growth. These findings provide new insights into naturally acquired anti-filarial immunity and the mechanisms shaping host-parasite interactions during reinfection, thereby reflecting the repeated parasite exposure that is characteristic of human filarial infections in endemic settings.