Epigenetic landscape of Leishmania-host interactions

Leishmaniasis is a complex immuno-metabolic infectious disease regulated by epigenetic mechanisms in both the parasite and host. Epigenetic modifications such as chromatin remodeling, histone post-translational modifications (PTMs), and non-coding RNAs (ncRNAs) modulate gene expression to promote parasite survival and alter host immune responses. This review highlights species-specific epigenetic changes across <i>Leishmania</i> species contributing to pathogenesis and explains how the parasite manipulates host immune signaling through epigenetic pathways, including co-infection and co-morbidity models. Host factors like nuclear factor of activated T cells 5 (NFAT5) and Src homology 2 domain-containing phosphatase-1 (SHP-1), along with parasite-derived proteins such as Su(var)3-9, enhancer of zeste [E(z)], trithorax (SET) proteins, and histones, are emerging as promising epigenetic therapeutic targets. Furthermore, histone PTMs and transcription factors are critical epigenetic modifications supporting parasite survival. Synthetic gene circuits can modulate host and parasite epigenomes. Synthetic biology enables the assembly of genetic parts and pools to engineer cells with novel biological functions. A structured literature review using Web of Science, PubMed, and Scopus was performed, using keywords like epigenetics of <i>Leishmania</i>, epigenetics alterations in host with leishmaniasis, <i>Leishmania</i> and comorbidity and disease-specific terms. This review underscores the future potential of epigenetics and synthetic biology-based strategies in controlling leishmaniasis.