Part of the work presented here was supported by a grant from the University of Saarland Medical Faculty (Homfor, to I.J.) and from the German Federal Ministry for Education and Science (BMBF) (grant #01 KI 07103 Skin Staph to M.H.). “
“Chaperone production is an essential step for proper folding of certain proteins. Accumulation of misfolded/unfolded proteins within the endoplasmic reticulum (ER) lumen triggers a signalling pathway named unfolded protein response (UPR). Upon activation,

the UPR pathway Dasatinib cost augments transcription of ER chaperones increasing protein folding, decreases protein translation to ameliorate the ER overload, increases protein degradation, and activates the apoptotic programme if all previous measures fail. In this review, we will cover the chaperones involved in folding of proteins related to the immune response, followed by an overview of the UPR pathway. Lastly, we will discuss data from this last decade that demonstrate how the improper 3-deazaneplanocin A activation of the UPR pathway has been uncovered as a mechanism responsible for failure to mount a proper immune response, both innate

and adaptive. The accumulation of unfolded/misfolded proteins within the endoplasmic reticulum (ER), followed by inability of the cell to cope with this excessive protein load defines the ER stress. The unfolded protein response (UPR) corresponds to the signalling pathway that cells have evolved in order to trigger those mechanisms that aim at properly folding and exporting intra-luminal protein load. This aim is achieved by means of (1) induction of molecular chaperones to increase the rate of protein folding; (2) attenuation of protein translation; (3) increased degradation of misfolded proteins; and ultimately, when all previous fail; (4) activation of apoptotic pathways for cell termination. In this review, we will cover some aspects of immunity-related proteins folding, followed by an overview of the activation and regulation steps of the UPR pathway. Lastly, we will describe the scenarios known so far in which improper protein folding was uncovered as a mechanism responsible for failure of a proper immune response. Pyruvate dehydrogenase This review will focus specifically in immune responses from the innate

system and B cells, so far characterized as being most sensitive to failure of activation of the UPR pathway. Chaperone production is an essential step for proper folding of certain proteins. ER chaperones bind to unfolded polypeptide chains while they are being synthesized, preventing them from aggregating and becoming non-functional. Some chaperones are important for proper assembly of macromolecular structures, as immunoglobulins, for example. Chaperones assist the folding and assembly of several macromolecules but are not components of the final structure. Chaperones are divided into three groups: chaperones of the heat-shock family, chaperone lectins, and substrate-specific chaperones (for an extensive review on chaperone classification see [1]).