["Danger theory"as a common mechanism of sarcoidosis induction by infectious and non- infectious factors - a role of environmental factors and autoimmunity].
2018
: In the light of modified the Matzinger's model of immune response, human heat shock proteins (hsp) as main "danger signals" tissue damage-associated molecular patterns (DAMPs) or/and microbial hsp 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 genetically changed PRR and persisting in genetically altered host phagocytes, generate increased release of both human and microbial hsp with their molecular and functional homology. High chronic spread of human and microbial hsp altering cytokines, co-stimulatory molecules, and Tregs expression, apoptosis, oxidative stress, induces the autoimmunity, considered in sarcoidosis. Regarding non-infectious causes of sarcoidosis, human hsp 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 hsp as DAMPs and/or microbial hsp 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.
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