Recognition of potential pathogenic microorganisms by the innate immune system is a function of a class of cellular receptors known as the pattern recognition receptors (PRRs), which include the toll-like receptors (TLRs). The innate system uses these receptors to recognize evolutionarily conserved molecular motifs, the pathogen associated molecular patterns (PAMPs) of infectious microbes. The TLRs represent an evolutionarily conserved signaling system that is a major determinant of the innate immune and inflammatory responses.Members of the TLR family, first discovered in <italic>Drosophila</italic>, are type 1 trans membrane receptors and in humans and mice, 11 TLRs have been identified with each member recognizing and responding to different microbial components. TLR2, in association with TLR1 and/or TLR6 induces signals after exposure to bacterial lipoproteins and peptide-glycans, whereas lipopolysaccharide (LPS) from Gram-negative bacteria signals through TLR4. Double stranded RNA stimulates TLR3, bacterial flagellin induces signaling through TLR5 and TLR9 mediates responses to the CpG motif of the bacterial DNA.Upon activation with the appropriate ligand, TLRs induce a range of responses including cell proliferation and production of various cytokines, chemokines or effector molecules including nitric oxide and reactive oxygen intermediates. TLRs harbor leucine-rich repeats (LRR) in the extracellular portion and a Toll/IL1 receptor (TIR) domain in the cytoplasmic portion. There are five TIR domain-containing adaptors (MyD88, TIRAP, TRIF, TRAM and SARM) that play significant role in TLR signaling.TLRs are good therapeutic targets in septic shock, asthma, inflammatory bowel disease and cancer. They are also used as vaccine adjuvants especially imidazoquinoline compounds such as Imiquimod and Resiquimod (R-848) that bind to TLR7 and TLR8.Preliminary evaluation of expression profiles of chicken TLRs in the heterophils and selected tissues of 20-weeks old White Leghorn (WLH) and indigenous chickens using reverse transcription polymerase chain reaction (RT-PCR) revealed that the indigenous birds expressed a greater repertoire of TLRs. TLR2 type1, TLR2 type 2, TLR3, TLR4, TLR5 and TLR 7 were all expressed in these birds while only TLR4 and TLR7 were expressed in the corresponding WLH chickens and that too, in only 37% of the birds. In case of Aseel (Indigenous chicken), the TLR repertoire was broad with 100% of the birds expressing all the TLRs tested. In the case of tissues, the differences between these two breeds were not very prominent. An understanding of the TLR expression repertoire is essential for more refined therapeutic interventions using TLR agonist and for its application as vaccine adjuvants.</sec></body></article></article></body></html>

JII

Journal of Immunology and Immunopathology

0972-0561

The Indian Society of Immunology & Immunopathology

jii-8-2-siip004

RESEARCH NOTE

Toll-like receptors - A link between innate and adaptive immunity

Raj

G. Dhinakar

Associate Professor

Department of Animal Biotechnology, Madras Veterinary College, Chennai – 600 007.

122006

828181

Recognition of potential pathogenic microorganisms by the innate immune system is a function of a class of cellular receptors known as the pattern recognition receptors (PRRs), which include the toll-like receptors (TLRs). The innate system uses these receptors to recognize evolutionarily conserved molecular motifs, the pathogen associated molecular patterns (PAMPs) of infectious microbes. The TLRs represent an evolutionarily conserved signaling system that is a major determinant of the innate immune and inflammatory responses.Members of the TLR family, first discovered in <italic>Drosophila</italic>, are type 1 trans membrane receptors and in humans and mice, 11 TLRs have been identified with each member recognizing and responding to different microbial components. TLR2, in association with TLR1 and/or TLR6 induces signals after exposure to bacterial lipoproteins and peptide-glycans, whereas lipopolysaccharide (LPS) from Gram-negative bacteria signals through TLR4. Double stranded RNA stimulates TLR3, bacterial flagellin induces signaling through TLR5 and TLR9 mediates responses to the CpG motif of the bacterial DNA.Upon activation with the appropriate ligand, TLRs induce a range of responses including cell proliferation and production of various cytokines, chemokines or effector molecules including nitric oxide and reactive oxygen intermediates. TLRs harbor leucine-rich repeats (LRR) in the extracellular portion and a Toll/IL1 receptor (TIR) domain in the cytoplasmic portion. There are five TIR domain-containing adaptors (MyD88, TIRAP, TRIF, TRAM and SARM) that play significant role in TLR signaling.TLRs are good therapeutic targets in septic shock, asthma, inflammatory bowel disease and cancer. They are also used as vaccine adjuvants especially imidazoquinoline compounds such as Imiquimod and Resiquimod (R-848) that bind to TLR7 and TLR8.Preliminary evaluation of expression profiles of chicken TLRs in the heterophils and selected tissues of 20-weeks old White Leghorn (WLH) and indigenous chickens using reverse transcription polymerase chain reaction (RT-PCR) revealed that the indigenous birds expressed a greater repertoire of TLRs. TLR2 type1, TLR2 type 2, TLR3, TLR4, TLR5 and TLR 7 were all expressed in these birds while only TLR4 and TLR7 were expressed in the corresponding WLH chickens and that too, in only 37% of the birds. In case of Aseel (Indigenous chicken), the TLR repertoire was broad with 100% of the birds expressing all the TLRs tested. In the case of tissues, the differences between these two breeds were not very prominent. An understanding of the TLR expression repertoire is essential for more refined therapeutic interventions using TLR agonist and for its application as vaccine adjuvants.</sec></body></article></article></body></html>