Fine-Tuning Immune Responses in Cutaneous Leishmaniasis: How <i>Leishmania major</i> Antigens Shape Th1/Th2 Differentiation

Introduction: Leishmaniasis, a widespread zoonotic disease caused by various species of the parasitic protozoan Leishmania, presents a significant global health challenge. Current treatment options have limitations, prompting research into alternative approaches. Utilizing parasite-derived antigens to stimulate and modulate the host’s immune system holds promise as a potential therapeutic strategy. This study investigates the role of Leishmania major excretory/secreted antigens (ESA) and lysate Leishmania antigens (LLA) in modulating Th1 and Th2 immune responses. Methods: Leishmania major parasites [MRHO/IR/75/ER] were cultured in NNN and RPMI1640 media. LLA and ESA were prepared and quantified for protein content. Subsequently, BALB/c mice were treated with LLA, ESA, and adjuvants (complete and incomplete Freund’s adjuvant), either alone or in combination. Cellular immune responses against parasite antigens were then evaluated. Results: The average weight of mice in the negative control group did not differ significantly from that of mice receiving adjuvant alone (P&gt;0.05). However, a significant difference was observed between the negative control group and the groups receiving ESA, LLA, or a combination of both (P&lt;0.05). Conclusion: The findings of this study suggest that ESA and LLA derived from Leishmania major play a role in modulating the immune response. The results indicate that the use of these antigens, alone or in combination with adjuvants, can impact mouse weight. While the negative control group did not show a significant difference compared to the adjuvant-only group, significant differences were observed between the negative control group and the groups receiving the antigens. These observations point to the potential of the investigated antigens to stimulate immune responses and could be considered for the development of therapeutic strategies against leishmaniasis. However, further studies are needed to fully elucidate the immunogenic mechanisms and to optimize the use of these antigens.