Local cytokine modulation and parasite visceralization during murine coinfection with Leishmania amazonensis and Schistosoma mansoni.

Coinfections involving helminths and protozoan parasites are frequent in endemic regions and can influence host immunity and disease outcomes. Although Schistosoma mansoni is known to modulate immune responses in several infectious and inflammatory diseases, its impact on Leishmania (Leishmania) amazonensis infection remains poorly understood. Here, we investigated how the timing of S. mansoni infection affects the progression of L. amazonensis disease in BALB/c mice. Two experimental settings were established: an early coinfection, in which S. mansoni infection occurred 15 days after L. amazonensis infection, before the development of cutaneous lesion (Leish(15)/Schisto); and a late coinfection, in which S. mansoni infection occurred 45 days after L. amazonensis infection, when lesions were already established (Leish(45)/Schisto). Early coinfection significantly reduced lesion size and footpad inflammation after 5-6 weeks, coinciding with the onset of S. mansoni egg laying and a shift toward Th2-polarized immune profile. Despite the occurrence of smaller lesions, parasite burden remained unchanged, indicating immune-mediated attenuation rather than enhanced parasite clearance. In contrast, late coinfection did not alter lesion progression but was associated with higher parasite burden. L. amazonensis did not affect schistosomiasis, although rare S. mansoni males exhibited atypical morphologies, suggesting systemic effects of chronic coinfection on worm physiology. Visceral dissemination of L. amazonensis occurred in both single- and coinfected mice but was more pronounced in coinfected animals, accompanied by tissue-specific cytokine modulation, particularly in the spleen. Collectively, our results suggest that the outcome of S. mansoni-L. amazonensis coinfection is strongly dependent on the timing and sequence of infection, orchestrated by temporal and immunological factors rather than direct parasite competition - such as disputes over host resources or occupation of shared tissue niches. These findings underscore the complexity of host-parasite-parasite interactions and highlight the importance of considering coinfection dynamics in the diagnosis and management of co-endemic diseases.