Leishmania spp. are obligatory intracellular parasites that primarily infect macrophages. The macrophage immune response plays a pivotal role in determining the control or progression of infection. “M1-like” macrophages mediate parasite clearance through the production of nitric oxide, pro-inflammatory cytokines, and reactive oxygen species, whereas “M2-like” macrophages contribute to infection progression by exerting anti-inflammatory effects. The capsular polysaccharides Glucuronoxylomannan (GXM) and glucuronoxylomannogalactan (GXMGal) from Cryptococcus neoformans are capable of immunomodulating the macrophage response. GXM exhibits immunoregulatory activity, whereas GXMGal induces a pro-inflammatory response. Although the activity of these polysaccharides has been studied in cryptococcosis, their immunomodulatory potential in other infectious models remains largely unexplored. Here, we investigated the effects of GXM and GXMGal on Leishmania major infection in murine peritoneal macrophages. Murine peritoneal macrophages were infected with L. major and, 24 h post-infection, treated with 50 μg of either GXM or GXMGal. Our data revealed that GXM treatment enhanced L. major infection, while GXMGal treatment had no significant effect on the parasitic load in infected macrophages.

Feline leishmaniasis is an emerging zoonotic disease, yet the cellular and immunological mechanisms underlying Leishmania infection in cats remain poorly understood. In this study, we established and characterized Fcwf-4 feline macrophages as an in vitro model of Leishmania amazonensis infection and investigated the immunomodulatory effects of glucuronoxylomannan (GXM), the major capsular polysaccharide of Cryptococcus neoformans. Fcwf-4 macrophages were infected with L. amazonensis promastigotes and evaluated at 2, 24, and 48 h post-infection. Parasite burden, macrophage viability, nitric oxide (NO), and reactive oxygen species (ROS) production were assessed in the presence or absence of GXM. Fcwf-4 macrophages supported L. amazonensis infection throughout the experimental period, with a progressive decrease in the infection index, indicating partial control of parasite burden over time. Notably, the presence of GXM increased the infection index without compromising macrophage viability, suggesting that enhanced parasite persistence resulted from immunomodulation rather than cytotoxicity. LPS stimulation enhanced NO and ROS production, whereas L. amazonensis infection selectively reduced NO production, indicating impairment of macrophage effector responses. Further, GXM suppressed ROS production, including basal ROS levels, suggesting an additional inhibitory effect on macrophage oxidative responses. Collectively, these findings provide experimental evidence that Fcwf-4 could be useful as a tool to study feline macrophage–Leishmania interactions in vitro and co-infection-associated immunomodulation.