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. 2022 Aug 18;13:949670. doi: 10.3389/fimmu.2022.949670

Figure 7.

Figure 7

Schematic illustration of the inflammatory and immune responses potentially regulated by exosomal miRNAs in the present study. The bacterial virulence factors such as flagellar, proteases, etc. facilitate the adhesion and invasion of bacteria to the host cell. Meanwhile, the bacterial virulence factors including flagellin, RNA, DNA, LPS, etc. are recognized by the host membrane PRRs (e.g. TLRs) or transported by bacterial OMVs into the host cytosol by endocytosis and then recognized by cytosolic PRRs (e.g. TLRs, NLRs). After pathogen recognition, signaling pathways involved in the regulation of inflammatory and immune responses were activated at both transcriptional and posttranscriptional levels (e.g. NF-κB, IRFs, MAPK), resulting the homeostasis of cytokine production. Moreover, the bacteria are able to compete for metal ions and affect the metabolic process of the host cell. The above-mentioned processes are potentially regulated by exosomal miRNAs after exosome uptake by endocytosis or other ways. For example, ZC3H12A can degrade IL-6 mRNA by binding to its 3’UTR on ER, which are counteracted by ARID5A, while the ZC3H12A mRNA could be inhibited by ssa-miR-146a-5p from the exosomes which have access to the ER. LPS, Lipopolysaccharide; PRRs, Pattern recognition receptors; TLRs, Toll-like receptors; OMVs, Outer membrane vesicles; NLRs, Domain-like receptors; NF-κB, Nuclear factor−κB; IRFs, Interferon-​regulatory factors; MAPK, Mitogen-activated protein kinase; IL-6, Interleukin-6; 3’UTR, 3’ Untranslated region; ER, Endoplasmic reticulum.