Fig. 2.

Schematic representation of the activation of various TLR signaling pathways leading to the development of cytokine storm and sepsis. The stimulation of TLR4 and TLR2 via their corresponding PAMPs activate a cascade of events, which results in the activation of NF-κB, p38 and JNK, CREB, and AP-1 etc. which regulates the synthesis and release of various pro-inflammatory cytokines (IL-1, IL-6, IL-12, IL-8, and TNF-α), anti-inflammatory cytokine (IL-10), and type 1 IFNs. The exaggerated levels of these inflammatory mediators develop cytokine storm during sepsis and other severe infections, including COVID-19. The patient develops multi-organ failure, including ALI and dies.