Recognition of microbes and damaged cells in inflammation
THE CONTEXT
Inflammation begins when cellular receptors and circulating proteins recognize microbes or necrotic cells.
Tissue sentinel cells
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Tissue-resident macrophages and dendritic cells are the principal sentinel cells. They detect foreign invaders or dead cells, ingest and destroy them, and initiate inflammatory reactions that recruit cells and proteins from blood.
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Receptors detect microbial products at the cell surface, in endosomes containing ingested microbes, and in the cytosol, where some microbes may survive.
Receptor systems and cytokines
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Activation of Toll-like receptors (TLRs) leads to production of cytokines that trigger inflammation.
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Cytosolic NOD-like receptors (NLRs) recruit and activate the inflammasome, a multiprotein complex that generates biologically active interleukin-1 (IL-1).
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NLRs recognize microbial products and indicators of cell damage, including leaked DNA and decreased cytosolic potassium.
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The resulting cytokine-induced inflammation eliminates microbes and dead cell debris.
Recognition in the circulation
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Microbes entering the circulation are recognized by plasma proteins, including antibodies and complement proteins.
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These proteins can destroy circulating microbes and enter tissue sites of infection, where they stimulate inflammatory reactions.