Type III Interferons (lambda) in Parasitic Infections: Balancing Mucosal Defense and Immune Modulation

Parasitic infections are a significant global health issue, with pathogens often entering the hosts through mucosal surfaces. Type III interferons (IFN-λ) are key mediators of immune responses in these infections. Produced mainly at epithelial barriers, IFN-λ induces a specific set of IFN-stimulated genes (ISGs) that boost antiviral and antimicrobial defense without causing widespread systemic inflammation. This review examines functions of IFN-λ diverse in parasitic infections, focusing on roles in antimicrobial responses and immune modulation. Understanding these effects may lead to new therapeutic strategies that leverage IFN-λ signaling to enhance host defenses while minimizing harmful inflammation. IFN-λ plays a nuanced role in parasitic infections. In Toxoplasma gondii, IFN-λ signaling in intestinal epithelial cells and neutrophils limits the spread of the parasite and enhances humoral immunity. In Cryptosporidium infections, IFN-λ reduces parasite loads and improves survival via STAT1-dependent pathways. However, in malaria, IFN-λ4 is associated with increased susceptibility to Plasmodium falciparum. In Leishmania donovani, IFN-λ3 may reduce parasite uptake in vitro, although in vivo administration could shift immune responses toward a Th2 profile, hindering parasite clearance. Elevated IFN-λ levels have been observed in helminth infections, suggesting their role in modulating inflammation and strengthening mucosal barriers. Understanding the complex effects of IFN-λ in parasitic infections may lead to new therapeutic approaches that enhance host defenses while reducing inflammation.