Figure 1. Interactions of stress proteins and cell surface TLR signaling pathways.

Engagement of cell surface TLR1, -2, -4, -5, or -6 initiates the MyD88-dependent signaling pathway, which results in activation of the downstream IKK and MKK signaling branches. Each of these branches induces expression of proinflammatory cytokines such as TNFα, IL-6, and IL-1β by the transcription factors NF-κB and AP-1. The TRIF-dependent signaling branch downstream of TLR4 results in expression of type I IFNs mediated by IRF3. The regulatory roles of stress proteins important in oxidative stress (yellow), heat shock response (green), UPR (blue), and DDR (pink) in these TLR signaling pathways are illustrated. →, stimulation; ↔, direct interaction; ⫞, inhibition.