Khan, Masood A.Gallo, Richard M.Brutkiewicz, Randy R.2020-05-182020-05-182010-05Khan, M. A., Gallo, R. M., & Brutkiewicz, R. R. (2010). Anthrax lethal toxin impairs CD1d-mediated antigen presentation by targeting the extracellular signal-related kinase 1/2 mitogen-activated protein kinase pathway. Infection and immunity, 78(5), 1859–1863. https://doi.org/10.1128/IAI.01307-09https://hdl.handle.net/1805/22796Lethal toxin (LT) is a critical virulence factor of Bacillus anthracis and an important means by which this bacterium evades the host's immune system. In this study, we demonstrate that CD1d-expressing cells treated with LT have reduced CD1d-mediated antigen presentation. We earlier showed an important role for the mitogen-activated protein kinase extracellular signal-regulated kinase 1/2 (ERK1/2) in the regulation of CD1d-mediated antigen presentation, and we report here that LT impairs antigen presentation by CD1d in an ERK1/2-dependent manner. Similarly, LT and the ERK1/2 pathway-specific inhibitor U0126 caused a decrease in major histocompatibility complex (MHC) class II-mediated antigen presentation. Confocal microscopy analyses revealed altered intracellular distribution of CD1d and LAMP-1 in LT-treated cells, similar to the case for ERK1/2-inhibited cells. These results suggest that Bacillus anthracis has the ability to evade the host's innate immune system by reducing CD1d-mediated antigen presentation through targeting the ERK1/2 pathway.en-USAttribution 4.0 InternationalAntigen presentationAntigens, BacterialAntigens, CD1dBacterial toxinsMAP Kinase Signaling SystemMitogen-activated protein kinasesArticle