Toll-like receptors (TLRs) are major components of the innate immune
system playing an important role in host defense against pathogens by recognizing a
wide variety of pathogen-associated molecular patterns (PAMPs).Till date, thirteen
mammalian TLR members (TLR1-13) have been identified, ten in human and thirteen
in mice. The human TLRs are further divided into two subgroups: six surface bound
(TLR 1, 2, 4, 5, 6 and 10) and four within the intracellular endosomal compartment
(TLR 3, 7, 8, and 9) of TLR-expressing cells. Extracellular TLRs identify structural
components of pathogens like lipopolysaccharides, peptidoglycan, βglucan etc.
Whereas endosomal TLRs are specific to pathogenic nucleic acids viz. double-stranded
RNA (dsRNA), single-stranded RNA (ssRNA) CpG ODN etc. These sensors are
expressed in a number of cell types including conventional dendritic cells (cDCs),
plasmacytoid DCs (pDCs), macrophages, and B cells. Interaction with specific
pathogenic antigens incites TLRs to trigger the transcription followed by synthesis of
pro-inflammatory cytokines. Both the groups of TLRs have been particularly
implicated in the pathogenesis of cancer, allergy and autoimmune disorders. However
the present chapter is focused on endosomal TLRs and their crucial role in
inflammation and related diseases. The initial part is focused on structural features of
TLRs, specific ligands and thereafter intracellular signaling arbitrating the release of
inflammatory mediators. In addition the role of endosomal TLRs in disease aggravation
is also discussed. Moreover, the inhibition of activation or ability of modulation of
these endosomal TLRs with specific ligands has also been illustrated as complementary
therapeutic agents to combat various human ailments.
Keywords: Cytokine, Disorders, Ectodomain, Endosome, Glycoproteins, Immune
system, Immunomodulation, Inflammation, Leucine rich repeats, Microorganisms,
Nucleic acid, Pattern recognition receptors, Therapeutics, Toll-like
receptors, Transmenbrane.
