The Regulatory Effect of Histone Deacetylase ( <scp>HDAC</scp> ) 1 and 2 on <scp>iNOS</scp> , <scp>IL</scp> ‐6, <scp>TNF</scp> ‐α and <scp>IL</scp> ‐10 Expression in Canine Macrophages Infected With <i>Leishmania infantum</i>

Zoonotic visceral leishmaniasis is caused by Leishmania (Leishmania) infantum. Dogs are considered the most critical urban reservoirs of L. (L.) infantum due to their high infection rate and direct transmission to humans. The parasite has developed mechanisms to evade the host's defence system by inhibiting macrophage activation, thereby allowing it to replicate and survive. Pathogens such as viruses and bacteria can modify the host's epigenome, thereby facilitating their survival. Cellular reprogramming leads to epigenetic alterations that modulate chromatin, modify histones and DNA methylation, disrupt normal progression and compromise the continuity of cell differentiation. Histone deacetylases (HDACs) remove lysine acetyl groups from histones, resulting in chromatin alteration and gene silencing. Histone acetyltransferases regulate their function. In this study, we analysed the involvement of HDAC-1 in the defen mechanisms of DH82 macrophages infected with L. infantum. We observed that L. infantum infection increases HDAC1 levels and expression. Silencing HDAC1 with siRNA and the pharmacological inhibitor NaB decreased parasite load and increased iNOS expression, associated with increased histone acetylation at the iNOS promoter. The pharmacological inhibitor NaB also decreased IL-6, IL-10 and TNF-α levels in the culture supernatant of DH82 macrophages infected with L. infantum. Together, these findings indicate that L. infantum-induced HDAC1 upregulation modulates the expression of key innate immune response genes, contributing to the establishment of infection in canine macrophages.