Abstract
Toll-like receptors (TLRs) sense microbial products and play an important role in innate immunity. Currently, 11 members of TLRs have been identified in humans, with important function in host defense in early steps of the inflammatory response. TLRs are present in the plasma membrane (TLR1, TLR2, TLR4, TLR5, TLR6) and endosome (TLR3, TLR7, TLR8, TLR9) of leukocytes. TLRs and IL-1R are a family of receptors related to the innate immune response that contain an intracellular domain known as the Toll-IL-1R (TIR) domain that recruits the TIR-containing cytosolic adapters MyD88, TRIF, TIRAP and TRAM. The classical pathway results in the activation of both nuclear factor κB and MAPKs via the IRAK complex, with two active kinases (IRAK-1 and IRAK-4) and two non-catalytic subunits (IRAK-2 and IRAK-3/M). The classical pro-inflammatory TLR signaling pathway leads to the synthesis of inflammatory cytokines and chemokines, such as IL-1β, IL-6, IL-8, IL-12 and TNF-α. In humans, genetic defects have been identified that impair signaling of the TLR pathway and this may result in recurrent pyogenic infections, as well as virus and fungi infections. In this review, we discuss the main mechanisms of microbial recognition and the defects involving TLRs.
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Abbreviations
- AD:
-
Autosomal dominant
- APCs:
-
Antigen-presenting cells
- BCG:
-
Bacillus Calmette-Guérin
- BTK:
-
Brutons’s tyrosine kinase
- CD62L:
-
CD62 ligand
- CNS:
-
Central nervous system
- CVID:
-
Common variable immunodeficiency
- DCs:
-
Dendritic cells
- dsRNA:
-
Double-stranded RNA
- EDA-ID:
-
Ectodermal dysplasia with immunodeficiency
- HClO:
-
Hypochlorous acid
- HO-1:
-
Heme oxygenase 1
- HSE:
-
Herpes simplex virus-encephalitis
- HSV-1:
-
Herpes simplex virus type 1
- IFN-γ:
-
Interferon-gamma
- IKK:
-
Inhibitor of NF-κB kinase complex
- IL-8:
-
Interleukin-8
- IRAK-4:
-
IL-1 receptor-associated kinase 4
- LPS:
-
Lipopolysaccharide
- LTA:
-
Lipoteichoic acid
- MALP-2:
-
Macrophage-activating lipopeptide-2
- MAPKs:
-
Mitogen-activated protein kinases
- MBL:
-
Mannose-binding lectin
- MyD88:
-
Myeloid differentiation factor 88
- NADPH:
-
Nicotinamide adenine dinucleotide oxidase
- NEMO:
-
NF-κB essential modulator
- NF-κB:
-
Nuclear factor kappaB
- NLRPs:
-
NOD leucine-rich repeat and pyrin domain containing proteins
- NLRs:
-
Leucine-rich repeat-containing receptors
- PAMPs:
-
Pathogen-associated molecular patterns
- PBMCs:
-
Peripheral blood mononuclear cells
- PDC:
-
Plasmacytoid DCs
- PIC:
-
Poly-riboinosinicribocytidylic acid
- PID:
-
Primary immunodeficiency diseases
- PMN:
-
Polymorphonuclear cells
- PRRs:
-
Pattern-recognition receptors
- RIG-I:
-
Retinoic acid-inducible gene I protein
- ssRNA:
-
Single-stranded RNA
- TIR:
-
Toll-IL-1R domain
- TIRAP:
-
TIR domain-containing adapter protein
- TLRs:
-
Toll-like receptors
- TRAM:
-
TRIF-related adapter molecule
- TRIF:
-
TIR domain-containing adapter-inducing IFN-β
- Xid:
-
X-linked immune deficiency
- XLA:
-
X-linked agammaglobulinemia
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Frazão, J.B., Errante, P.R. & Condino-Neto, A. Toll-Like Receptors’ Pathway Disturbances are Associated with Increased Susceptibility to Infections in Humans. Arch. Immunol. Ther. Exp. 61, 427–443 (2013). https://doi.org/10.1007/s00005-013-0243-0
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DOI: https://doi.org/10.1007/s00005-013-0243-0