Article
Bacterial stimulation upregulates the surface expression of the stress protein gp96 on B cells in the frog Xenopus.
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Cell Stress and Chaperones (impact factor:
3.01).
02/2003;
8(3):265-71.
pp.265-71
Source: PubMed
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Citations (0)
- Cited In (2)
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Article: Bap, a biofilm matrix protein of Staphylococcus aureus prevents cellular internalization through binding to GP96 host receptor.
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ABSTRACT: The biofilm matrix, composed of exopolysaccharides, proteins, nucleic acids and lipids, plays a well-known role as a defence structure, protecting bacteria from the host immune system and antimicrobial therapy. However, little is known about its responsibility in the interaction of biofilm cells with host tissues. Staphylococcus aureus, a leading cause of biofilm-associated chronic infections, is able to develop a biofilm built on a proteinaceous Bap-mediated matrix. Here, we used the Bap protein as a model to investigate the role that components of the biofilm matrix play in the interaction of S. aureus with host cells. The results show that Bap promotes the adhesion but prevents the entry of S. aureus into epithelial cells. A broad analysis of potential interaction partners for Bap using ligand overlayer immunoblotting, immunoprecipitation with purified Bap and pull down with intact bacteria, identified a direct binding between Bap and Gp96/GRP94/Hsp90 protein. The interaction of Bap with Gp96 provokes a significant reduction in the capacity of S. aureus to invade epithelial cells by interfering with the fibronectin binding protein invasion pathway. Consistent with these results, Bap deficient bacteria displayed an enhanced capacity to invade mammary gland epithelial cells in a lactating mice mastitis model. Our observations begin to elucidate the mechanisms by which components of the biofilm matrix can facilitate the colonization of host tissues and the establishment of persistent infections.PLoS Pathogens 08/2012; 8(8):e1002843. · 9.13 Impact Factor -
Article: Molecular and cellular requirements for enhanced antigen cross-presentation to CD8 cytotoxic T lymphocytes.
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ABSTRACT: MHC class I-mediated cross-priming of CD8 T cells by APCs is critical for CTL-based immunity to viral infections and tumors. We have shown previously that tumor-secreted heat shock protein gp96-chaperoned peptides cross prime CD8 CTL that are specific for genuine tumor Ags and for the surrogate Ag OVA. We now show that tumor-secreted heat shock protein gp96-chaperoned peptides enhance the efficiency of Ag cross-priming of CD8 CTL by several million-fold over the cross-priming activity of unchaperoned protein alone. Gp96 also acts as adjuvant for cross-priming by unchaperoned proteins, but in this capacity gp96 is 1000-fold less active than as a peptide chaperone. Mechanistically, the in situ secretion of gp96-Ig by transfected tumor cells recruits and activates dendritic cells and NK cells to the site of gp96 release and promotes CD8 CTL expansion locally. Gp96-mediated cross-priming of CD8 T cells requires B7.1/2 costimulation but proceeds unimpeded in lymph node-deficient mice, in the absence of NKT and CD4 cells and without CD40L. Gp96-driven MHC I cross-priming of CD8 CTL in the absence of lymph nodes provides a novel mechanism for local, tissue-based CTL generation at the site of gp96 release. This pathway may constitute a critically important, early detection, and rapid response mechanism that is operative in parenchymal tissues for effective defense against tissue damaging antigenic agents.The Journal of Immunology 09/2007; 179(4):2310-7. · 5.79 Impact Factor
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Keywords
active surface expression
adaptive immune system
amplify immune responses
ancestral immunological role
antigen-presenting cells
B cells
certain cell types
endoplasmic reticulum resident protein
gp96 surface expression
heat-killed bacteria
heat-killed gram-negative bacteria
immune cells
messenger ribonucleic acid
natural killer cells
purified lipopolysaccharide
Purified Xenopus B cells
surface protein expressions
T cells
vertebrate taxon
vitro stimulation