Type I Interferons, Autophagy and Host Metabolism in Leprosy
Abstract
For those with leprosy, the extent of host infection by Mycobacterium leprae and the progression of the disease depend on the ability of mycobacteria to shape a safe environment for its replication during early interaction with host cells. Thus, variations in key genes such as those in pattern recognition receptors (NOD2 and TLR1), autophagic flux (PARK2, LRRK2, and RIPK2), effector immune cytokines (TNF and IL12), and environmental factors, such as nutrition, have been described as critical determinants for infection and disease progression. While parkin-mediated autophagy is observed as being essential for mycobacterial clearance, leprosy patients present a prominent activation of the type I IFN pathway and its downstream genes, including OASL, CCL2, and IL10. Activation of this host response is related to a permissive phenotype through the suppression of IFN-γ response and negative regulation of autophagy. Finally, modulation of host metabolism was observed during mycobacterial infection. Both changes in lipid and glucose homeostasis contribute to the persistence of mycobacteria in the host. M. leprae-infected cells have an increased glucose uptake, nicotinamide adenine dinucleotide phosphate generation by pentose phosphate ...Continue Reading
References
Convergence of IL-1beta and VDR activation pathways in human TLR2/1-induced antimicrobial responses.
Host genotype-specific therapies can optimize the inflammatory response to mycobacterial infections.
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