Fig. 1.

NLR-dependent regulation of MHC class I antigen presentation. (A) NLRC5 induces chromatin remodeling and recruitment of transcription factors, leading to the transactivation of MHC class I, and other related genes in the MHC class I antigen-presentation pathway, including LMP2, LMP7, TAP1, and β2-microglobulin. (B) Activation of the NLRP3 inflammasome and its effector caspase-1 acts on the NADPH oxidase NOX2 to induce phagosome acidification in response to microbial infection. This process negatively impacts cross-presentation. (C) NOD1 and NOD2 activation by peptidoglycan (PGN) significantly augments DC-mediated cross-presentation via upregulation of intracellular components, such as TAP, SEC61, and calnexin, for MHC class I dependent antigen presentation and co-stimulatory molecules expression. In addition, early activation of NOD2 signaling alone or in combination with TLR2 may be required for stabilisation of the immunoproteasome and promote cross-presentation during an early phase of pathogen handling. (D) PGN pre-treatment, prior to antigen encounter, leads to progressive inhibition of cross-presentation over time, with almost complete inhibition after 18 h.