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Figure 2. Schematic figure. Cooperative networks regulate inflammatory responses (1). Single agonists with more than one TLR specificity (e.g., viral activation of TLR3 and TLR4) or exposure to multiple TLR agonists (e.g., at sites of tissue damage where mRNA and tissue breakdown products are released) activate TLRs on resident monocytes (e.g., TLR4 or TLR7/8) and tissue cells (TLR3) (2). Stimulation of tissue leukocytes causes the release of mediators acting on tissue cells, and results in a synergistic proinflammatory reaction characterized by the production of large amounts of cytokines from activated tissue cells (3). Cytokine production, principally by tissue cells, results in the recruitment of a range of leukocytes (4). Survival factors released by monocytes regulate not only activation of tissue cells, but also the survival of recruited leukocytes such as neutrophils. Once these are withdrawn, inflammation can resolve by induction of leukocyte apoptosis.
