Sirtuins: Key pieces in the host response to pathogens' puzzle

Author(s)

Silva, Rafael de Freitas e ; Bassi, Gabriela ; Camara, Niels Olsen Saraiva ; Moretti, Nilmar Silvio

• Document type: Journal article
• Source: Molecular Immunology; v. 160, p. 11-pg., 2023-07-10.

Abstract

Global warming is changing the distribution of different pathogens around the globe, and humans are more susceptible to new or re-emerging infections. The human response to microbes is complex and involves different mechanisms of the immune system. Regulation of gene expression of immunity genes and of metabolism of immune cells are essential in this process. Both mechanisms could be regulated by protein lysine acetylation that will control chromatin structure affecting gene expression or key enzyme activity involved in cellular processes. Protein acetylation is crucial for the immunity and involves two families of enzymes: lysine acetyltransferases (KATs), which will promote protein acetylation, and lysine deacetylases (KDACs) that will reduce this modification. Lysine deacetylases are divided into Zinc-dependent or HDACs and NAD+ -dependent, or Sirtuins. These enzymes are in the nucleus, cytosol, and mitochondria of mammalian cells affecting different cellular pathways, such as metabolism, gene expression, DNA repair, cell proliferation, and apoptosis, opening the opportunity to explore these proteins as drug targets in different diseases, including cancer and neurodegenerative illness. Although widely explored in chronic diseases, very little is known about the role of Sirtuins during host response against microbes' infection. In this review we aim to explore the most recent literature evidencing a role for these enzymes during host responses to viruses, bacterial and protozoan infections, pointing out how these proteins can be manipulated by these pathogens to progress in the infection. Moreover, we will uncover the potential of host KDACs as therapeutic targets to prevent infections by activating effector immune functions. (AU)

• FAPESP's process: 18/09948-0 - Study of protein acetylation in Leishmania
• Grantee: Nilmar Silvio Moretti
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/07870-4 - Mechanisms of trypanosomatid adaptation to hosts through the control of transcription, protein synthesis and secretion of extracellular vesicles
• Grantee: Ana Claudia Trocoli Torrecilhas
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 22/03075-0 - Unraveling the regulatory mechanisms of host-parasite interaction of Leishmania: focus on post-transcriptional and post-translational changes
• Grantee: Nilmar Silvio Moretti
• Support Opportunities: Research Grants - Initial Project