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Microbial and human heat shock proteins as ‘danger signals’ in sarcoidosis
Authors:Anna Dubaniewicz
Affiliation:Department of Pneumology, Medical University of Gdansk, Debinki 7 St., 80-211 Gdansk, Poland
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.
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    , 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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