Microbial and human heat shock proteins as ‘danger signals’ in sarcoidosis |
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Authors: | Anna Dubaniewicz |
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Affiliation: | Department of Pneumology, Medical University of Gdansk, Debinki 7 St., 80-211 Gdansk, Poland |
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Abstract: | In the light of the Matzinger’s model of immune response, human heat shock proteins (HSPs) as main ‘danger signals’ (tissue damage-associated molecular patterns-DAMPs) or/and microbial HSPs as pathogen-associated molecular patterns (PAMPs) recognized by pattern recognition receptors (PRR), may induce sarcoid granuloma by both infectious and non-infectious factors in genetically different predisposed host. Regarding infectious causes of sarcoid models, low-virulence strains of, e.g. mycobacteria and propionibacteria recognized through changed PRR and persisting in altered host phagocytes, generate increased release of both human and microbial HSPs with their molecular and functional homology. High chronic spread of human and microbial HSPs altering cytokines, co-stimulatory molecules, and Tregs expression, apoptosis, oxidative stress, induces the autoimmunity, considered in sarcoidosis. Regarding non-infectious causes of sarcoidosis, human HSPs may be released at high levels during chronic low-grade exposure to misfolding amyloid precursor protein in stressed cells, phagocyted metal fumes, pigments with/without aluminum in tattoos, and due to heat shock in firefighters. Therefore, human HSPs as DAMPs and/or microbial HSPs as PAMPs produced as a result of non-infectious and infectious factors may induce different models of sarcoidosis, depending on the genetic background of the host. The number/expression of PRRs/ligands may influence the occurrence of sarcoidosis in particular organs. |
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Keywords: | AIM, absent in melanoma Ag, antigen ALR, AIM2-like receptor APC, antigen presenting cell CLR, C-type lectin receptor DAMP, damage-associated molecular pattern DC, dendritic cell HMGB1, high mobility group box1 HSPs, heat shock proteins IFN, interferon IL, interleukin LPS, lipopolysaccharide LRR, leucine-rich repeat Mtb-HSPs, mycobacterial HSPs MBP, mannose-binding protein miRNA, microRNA Mø , monocyte/macrophage NALP, natch domain-, leucine-rich repeat-, and pyrin-containing domain NLRP3, NOD-, LRR- and pyrin-domain containing 3 NLR, nucleotide oligomerization domain (NOD)-like receptor NOD, nucleotide binding and oligomerization domain PAMP, pathogen-associated molecular pattern PRR, pattern-recognition receptor PS, phosphatidylserine PTP, protein tyrosine phosphatase RAGE, receptor for advanced glycation endproducts RIG-I, retinoic acid-inducible gene I RLR, RIG-I-like receptor ROS, reactive oxygen species TLR, Toll-like receptor TREM, triggering receptor expressed on myeloid cells |
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