Down‐Regulation of gp96 by Orientia tsutsugamushi

Abstract

gp96 plays a central role in innate as well as acquired immunity, maturation and chemotaxis of dendritic cells, Ab production, and cross-priming, and is a peptide acceptor in endoplasmic reticulum and an accessory to peptide loading of MHC class I molecules. The remarkable conservation of essential immunological properties of gp96 suggests their important roles during the evolution of the immune system. Considering their importance in immunity, immune evasion mechanisms of pathogens by modulating gp96 expression have been speculated. By differential display PCR, we observed that obligate intracellular bacteria, Orientia tsutsugamushi, inhibit gp96 expression of a macrophage cell line, J774A.1. Not only gp96 transcripts but also protein was lower than for null-infected cells. The down-regulation was also consistent in an endothelial cell line, HMEC-1, and in murine peritoneal cells. These data support the idea that gp96 may be one of the target molecules for the immune evasion by intracellular bacteria.

Genes differentially expressed in oropharyngeal tonsils and mandibular lymph nodes of tuberculous and nontuberculous European wild boars naturally exposed toMycobacterium bovis

“…Antigen presentation was differentially regulated in wild boars in this study. The MHC-I and MHC-II pathways, which play a central role in innate as well as in acquired immunity, may be one of the target molecules for the immune evasion by mycobacteria and other intracellular bacteria (Zügel et al, 2001;Cho et al, 2004;Doody et al, 2004). Infection with mycobacteria affects MHC-I and MHC-II antigen processing (Gercken et al, 1994;Noss et al, 2000;Weiss et al, 2001).…”

Sub-proteomic study on macrophage response to Candida albicans unravels new proteins involved in the host defense against the fungus

“…In our model of interaction, we have detected a decrease in Hsp90b1 (GP96), Pdia3, α-SNAP, GRP78 and Pdia1 (PDI), all of them necessary for the development of a correct immune response, and an increase in Ptpn6 (SHP-1), a negative controller of both innate and acquired immune cytokine signaling [46]. Hsp90b1 (GP96) acts as chaperone for TLR receptors in macrophages thus being necessary for the development of antimicrobial response [63], it has been described as a target for an intracellular bacteria, Orientia tsutsugamushi [64], thus, the same can be happening for C. albicans. Mutant mice lacking Pdia3 have defects in the MHC class I peptide-loading complex assembly [65], and GRP78 and Pdia1 seem to be necessary for antibody folding [66].…”

Listeria monocytogenes Triggers the Cell Surface Expression of Gp96 Protein and Interacts with Its N Terminus to Support Cellular Infection

“…Gp96 plays an important role in pathogenesis, and its expression is directly modulated by different pathogens such as O. tsutsugamushi (25) and rotavirus (30). Thus, we investigated whether Listeria interferes with Gp96 expression during infection.…”

“…Bap-Gp96 interaction provokes a significant reduction in the capacity of S. aureus to invade epithelial cells by interfering with the fibronectin-binding protein invasion pathway (24). Orientia tsutsugamushi and rotavirus directly modulate the expression of Gp96, disturbing innate and adaptive immune responses and thus providing the appropriate environment for pathogen survival and proliferation (25,26).…”