Toll-like receptors and their role in experimental models of microbial infection

Abstract

Effective host defense against microbial infection depends upon prompt recognition of pathogens, activation of immediate containment measures, and ultimately the generation of a specific and definitive adaptive immune response. The innate immune system of the host is responsible for providing constant surveillance against infection; when confronted by pathogens it deploys a series of rapidly acting antimicrobial effectors while simultaneously instructing the adaptive immune system as to the nature and context of the infectious threat. Pathogen recognition and activation of innate immunity is mediated by members of the Toll-like receptor (TLR) family through detection of conserved microbial structures that are absent from the host. Experimental models of infection using TLR-deficient mice, as well as limited human studies, have clearly demonstrated the critical role of TLRs in host defense against most major groups of mammalian pathogens.

MyD88-independent activation of a novel actin-Cdc42/Rac pathway is required for Toll-like receptor-stimulated phagocytosis

“…Ligation of TLRs can elicit activation of conserved inflammatory pathways, culminating in the activation of the MAP kinase signaling pathways and IKK complexes, which transduce various upstream signals to the activation of AP-1 and NF-kB transcription factors [22]. Recent accumulating evidence has shown that TLRs are also involved in phagocytosis by helping phagocytes sense bacteria or their components [23,24]. Consistent with that, we have provided evidence to show that ligation of TLR4 can enhance phagocytosis of gram-negative bacteria E. coli and nonbacterial targets such as dextran, while exhibiting minimal effects on nonbacterial targets such as latex beads.…”

Innate immunity in aging: impact on macrophage function

“…1). Microbes, microbial products and pharmaceutical compounds that are ligands for TLR2, 3, 4, 5, 6, 7, 8, 9 and 11 have been identified (for reviews see Qureshi & Medzhitov, 2003;Takeda et al ., 2003;Underhill, 2003). TLR1 and 2, and 2 and 6 recognize the cell wall components of Gram-positive bacteria and yeast, whereas TLR4 recognizes the predominant Gram-negative bacterial product, lipopolysaccharide (LPS), RSV-F protein and endogenous ligands such as several heat shock proteins, beta defensin 2 and hyaluronic acid (Biragyn et al ., 2002;Termeer et al ., 2002;Vabulas et al ., 2002).…”

Lipopolysaccharide and Double-stranded RNA Up-regulate Toll-like Receptor 2 Independently of Myeloid Differentiation Factor 88

“…Different pathogen-associated molecular patterns are recognized by different TLRs. TLR4 recognizes enterobacterial lipopolysaccharide (LPS) (6,7). TLR3 recognizes double-stranded RNA (dsRNA) and the viral dsRNA mimic, synthetic polyinosine-polycytidylic acid (poly(I-C)) (8), and TLR5 initiates responses toward flagellin (9).…”