Going ballistic: Leishmania nuclear subversion of host cell plasticity. Issue 3 (March 2022)

• Record Type: Journal Article
• Authors: Lecoeur, Hervé; Prina, Eric; Gutiérrez-Sanchez, Maria; Späth, Gerald F.
• Is Part Of: Trends in parasitology. Volume 38:Issue 3(2022)
• Page Start: 205
• Page End: 216
• Publication Date: 2022-03
• Subjects: Leishmania -- macrophage -- dendritic cell -- epigenetic regulation -- transcriptional control -- transcription factor; Parasitology -- Periodicals; Parasitology -- Periodicals; Biology -- Periodicals; Parasitology; Biology; Parasitologie -- Périodiques; Online resources; 571.999
• DOI: 10.1016/j.pt.2021.09.009
• Languages: English
• ISSNs: 1471-4922

Abstract

Abstract : Intracellular parasites have evolved intricate strategies to subvert host cell functions for their own survival. These strategies are particularly damaging to the host if the infection involves immune cells, as illustrated by protozoan parasites of the genus Leishmania that thrive inside mononuclear phagocytic cells, causing devastating immunopathologies. While the impact of Leishmania infection on host cell phenotype and functions has been well documented, the regulatory mechanisms underlying host cell subversion were only recently investigated. Here we summarize the current knowledge on how Leishmania infection affects host nuclear activities and propose thought-provoking new concepts on the reciprocal relationship between epigenetic and transcriptional regulation in host cell phenotypic plasticity, its potential subversion by the intracellular parasite, and its relevance for host-directed therapy. Highlights: Phenotypic plasticity of macrophages (Mϕs) and dendritic cells (DCs) enables these cells to adapt their immune functions to local tissue microenvironment changes. Leishmania exploits Mϕ and DC phenotypic plasticity to establish permissive conditions for intracellular survival and chronic infection. Mϕ polarization and DC maturation result from a complex regulatory relationship between epigenetic and transcriptional gene expression controls. Leishmania infection changes the host cell epigenetic and transcription factor landscapes, resulting in the expression of a unique, anti-inflammatory host cell phenotype. Our review provides an overview of Leishmania subversion strategies that hijack epigenetic and transcriptional control in infected Mϕs and DCs. New venues for host-directed therapy are proposed to foster host antimicrobial functions.