Impact of co-infection with Plasmodium berghei ANKA in Leishmania major-parasitized mice on immune modulation and cutaneous leishmaniasis

Abstract

Background Malaria and leishmaniasis are vector-borne diseases responsible for a significant number of deaths worldwide. Despite the co-endemicity of these diseases in regions with tropical and subtropical climates, our understanding of the complex interplay between Plasmodium spp. and Leishmania spp. co-infections on host immune response and resultant disease outcomes remains limited. Methodology/Principal findings This study employs C57BL/6 mice co-infected with Leishmania major and Plasmodium berghei ANKA, well-established models of cutaneous leishmaniasis and experimental cerebral malaria, respectively. Our findings demonstrate that an acute infection with P. berghei ANKA mitigates the progression of ongoing cutaneous leishmaniasis, as evidenced by a reduction in lesion size and parasite burden in the dermis of L. major-infected mice. Co-infection also led to elevated serum levels of TNF compared to the levels observed in mice infected with L. major alone, which may contribute to a more effective control of the Leishmania parasite. Furthermore, co-infected mice exhibited reduced recruitment of activated T cells and inflammatory monocytes to the site of L. major infection. As inflammatory monocytes can be exploited by Leishmania as host cells that support parasite replication, their reduced infiltration may limit parasite growth. This diminished cellular infiltration is likely to contribute to reduced local inflammation, thereby limiting tissue damage and resulting in smaller lesion size. Conclusions/Significance These findings elucidate the potential cross-regulation of immune responses in co-infections, underscoring the necessity to consider co-infecting pathogens in disease management and therapeutic strategies in endemic areas.