Protective Role of Phosphoenolpyruvate Carboxykinase in Controlling Cutaneous Leishmaniasis

Cutaneous leishmaniasis (CL) is a neglected public health problem in developing countries including Iran. CL is caused by different species of Leishmania parasites and results in morbidity and complications in patients with active lesions. Since protozoa are intracellular parasites, cellular immunity plays an essential role in controlling the infection. Cellular immunity is induced immediately after the infection and persists for many years after recovery. Studies over the past decades have identified the important role of CD4+ T cells and their T-helper subtypes in the immune response to CL. Finding antigens capable of producing Th1-dominant immune responses can play an effective role in preventing CL. This study examines the protective role of phosphoenolpyruvate carboxykinase (PEPCK), a critical enzyme for protozoan survival and reproduction. The potential of targeting PEPCK for the development of novel prevention strategies against Chagas disease is explored. Detailed findings presented herein underscore the critical role of PEPCK as an immunogenic antigen in parasite metabolism, gluconeogenesis, and energy homeostasis. Notably, the elimination of PEPCK alters parasite metabolic activity and attenuates Leishmania pathogenicity. These results position PEPCK as a promising vaccine candidate and therapeutic target for CL, pending further validation.Cutaneous leishmaniasis (CL) is a neglected public health problem in developing countries including Iran. CL is caused by different species of Leishmania parasites and results in morbidity and complications in patients with active lesions. Since protozoa are intracellular parasites, cellular immunity plays an essential role in controlling the infection. Cellular immunity is induced immediately after the infection and persists for many years after recovery. Studies over the past decades have identified the important role of CD4+ T cells and their T-helper subtypes in the immune response to CL. Finding antigens capable of producing Th1-dominant immune responses can play an effective role in preventing CL. This study examines the protective role of phosphoenolpyruvate carboxykinase (PEPCK), a critical enzyme for protozoan survival and reproduction. The potential of targeting PEPCK for the development of novel prevention strategies against Chagas disease is explored. Detailed findings presented herein underscore the critical role of PEPCK as an immunogenic antigen in parasite metabolism, gluconeogenesis, and energy homeostasis. Notably, the elimination of PEPCK alters parasite metabolic activity and attenuates Leishmania pathogenicity. These results position PEPCK as a promising vaccine candidate and therapeutic target for CL, pending further validation.