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. 2021 Jan 29;9(2):102. doi: 10.3390/vaccines9020102

Figure 2.

Figure 2

Signaling pathways of obese/T2D cell, of critical COVID-19 cases. Obese and T2D patients have already activated inflammatory pathways. SARS-CoV-2 entry though ACE2 receptor, can alters ACE2/MasR1 axis inducing MAPK6 activation, triggering pyroptosis with high IL-1 production (cytokine storm). Uptake of viral antigens by intracellular Toll Like Receptors (TLR 7/8) can signal through NF-κB pathway, resulting in more inflammatory cytokine production (IL-1β, IL-6, IL-8, IL-18, CCL-2, and TNF-α) (cytokine storm). In addition, viral RNA can induce NLRP3 activation resulting in secretion of IL-1β (inflammasome), leading to further activated inflammation. Excessive inflammatory cytokines (IL-1/IL-6) can block IFN type 1 production. MAPK: mitogen-activated protein kinase, IL: Interleukins, ILR: Interleukins receptor, TNF: Tumor necrosis factor, BAX: BCL2-associated X genes, JNK: c-Jun N-terminal kinase, IRAK-2: Interleukin-1 receptor-associated kinase 2, EGRs: Early response genes, NF-κB: nuclear factor kappa B, TLR: toll-like receptor, CCL2: C-C motif chemokine ligand 2, ROS: Reactive oxygen species, mir146a: microRNA-146a, NLRP3: NLR family pyrin domain containing 3, ASC: Adaptor protein. Created with BioRender.com.