Toll-like receptor signaling in the lysosomal pathways.
The lysosomal pathway digests material received by two main routes, phagocytosis and autophagy. Cells use phagocytosis to ingest extracellular particles by invaginations of the plasma membrane. In autophagy, a double membrane structure isolates portions of the cytoplasm to target it for degradation. During infection, phagocytes use both of these cellular functions to restrict microbial replication and at the same time to orchestrate an appropriate response against the invader. Toll-like receptor recognition of a pathogen initiates an innate immune response against the pathogen that includes production of inflammatory cytokines, upregulation of costimulatory molecules to prime an adaptive immune response, and activation of phagocytosis and autophagy. Signaling through this family of receptors also produces a hybrid response in which proteins that participate in autophagy are recruited to phagosomes, resulting in expedited microbial elimination. In this review, we discuss recent views on how Toll-like receptors direct microbes to final destruction by regulating the different pathways that lead to the lysosome.
Sanjuan
Miguel A
MA
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105-3678, USA.
Milasta
Sandra
S
Green
Douglas R
DR
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001343:Autophagy / Q000235:genetics / Q000276:immunology*; D000071192:Autophagy-Related Protein 12; D006706:Homeostasis; D006801:Humans; D007239:Infections / Q000276:immunology; D008247:Lysosomes / Q000276:immunology / Q000378:metabolism*; D008561:Membrane Fusion / Q000276:immunology; D008869:Microtubule-Associated Proteins / Q000276:immunology / Q000378:metabolism; D010588:Phagosomes / Q000276:immunology / Q000378:metabolism*; D011494:Protein Kinases / Q000276:immunology; D021381:Protein Transport / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*
C466624:ATG12 protein, human; D000071192:Autophagy-Related Protein 12; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D051193:Toll-Like Receptors; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases