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Signaling Pathways title  Toll-like receptors signaling pathway

Toll-like receptors (TLRs) are integral membrane bound receptors that are vital for innate immunity and help to shape the adaptive immune response. These receptors are triggered by a variety of pathogen-associated molecular patterns (PAMPs), and danger-associated molecular patterns (DAMPs) (1).

Toll-like-receptors-mechanism

 
Generalized structure and signaling mechanisms of Toll-like receptors (1)
.

Signaling Pathways title  Roles of activated TLRs

  • Generate robust anti-microbial and pro-inflammatory responses at sites of possible infection or danger.
  • Trigger the release of anti-microbial peptides, diverse arrays of cytokines and chemokines and reactive oxygen species.
  • Induce cellular responses, such as phagocytosis and macropinocytosis, for increased uptake from the surrounding milieu and pathogen ingestion, whereas TLR-mediated cell survival, death and proliferation responses all contribute to an expansive adaptive immune response (2).

Signaling Pathways title  Toll Like Receptors and diseases

    TLRs are involved in a wide spectrum of diseases (1) :
  • Chronic pulmonary obstructive disease (COPD)
  • Autoimmune disease like Rheumatoid arthritis, Systemic Lupus Erythematosus and Sjogren’s syndrome.
  • TLRs participation in cancers acts as double-edge swords; their activation can regress the tumor growth or conversely promote the tumor cells. TLRs participates in breast cancer (3), lung cancer, neuroblastoma, colorectal cancer, thyroid carcinomas (4), hepatocellular, nasopharyngeal and prostate cancer (5).

(1) Anwar, M. A et al. Recent clinical trends in Toll-like receptor targeting therapeutics. Medicinal research reviews, (2019) 39(3), 1053–1090.
(2) Luo L et al. Signalling, sorting and scaffolding adaptors for Toll-like receptors. J Cell Sci. (2019) 30;133(5).
(3) Shi, S et al. Expression profile of Toll‑like receptors in human breast cancer. Molecular medicine reports. (2020) 21(2):786-794.
(4) Mokhtari Y et al. Toll-like receptors (TLRs): An old family of immune receptors with a new face in cancer pathogenesis. J Cell Mol Med. (2020) 25(2):639-651.
(5) Setrerrahmane S & Xu H. Tumor-related interleukins: old validated targets for new anti-cancer drug development. Mol Cancer. (2017) 19;16(1):153.
(6) Ou T et al. The Pathologic Role of Toll-Like Receptor 4 in Prostate Cancer. Front Immunol. (2018) 6;9:1188.
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