title: Anthrax lethal toxin impairs CD1d-mediated antigen presentation by targeting the extracellular signal-related kinase 1/2 mitogen-activated protein kinase pathway.
abstract: Lethal 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.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, 950 W. Walnut St., Indianapolis, IN 46202-5181, USA.
authors.forename: Masood A
authors.initials: MA
authors.lastname: Khan
authors.forename: Richard M
authors.initials: RM
authors.lastname: Gallo
authors.forename: Randy R
authors.initials: RR
authors.lastname: Brutkiewicz
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D000942:Antigens, Bacterial / Q000276:immunology*; D055610:Antigens, CD1d / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology*; D002460:Cell Line; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D020935:MAP Kinase Signaling System; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000942:Antigens, Bacterial; D055610:Antigens, CD1d; D001427:Bacterial Toxins; D000949:Histocompatibility Antigens Class II; C030325:anthrax toxin; D020928:Mitogen-Activated Protein Kinases