TY - JOUR
T1 - TLT2 potentiates neutrophil antibacterial activity and chemotaxis in response to G protein-coupled receptor-mediated signaling
AU - Halpert, Matthew M.
AU - Thomas, Kimberly A.
AU - King, R. Glenn
AU - Justement, Louis B.
PY - 2011/9/1
Y1 - 2011/9/1
N2 - Receptors encoded within the Trem locus have been shown to play an important role in modulating the cellular response to pattern recognition receptor signaling. TREM-like transcript 2 (TLT2) is a member of the Trem locus that is conserved in mouse and human. TLT2 exhibits a unique expression pattern in that it is expressed on cells of the myeloid and lymphoid lineage, suggesting that it plays a role in both innate and adaptive immunity. In this work, studies reveal that TLT2 plays an important role in potentiating neutrophil antibacterial activity and chemotaxis. TLT2 ligation enhances the neutrophil response to the formylated peptide FMLF, leading to increased reactive oxygen species production, degranulation, and chemotaxis. Moreover, TLT2 has the ability to specifically potentiate neutrophil activation and chemotaxis in response to a range of agonists that bind to G protein-coupled receptors, as it does not potentiate the response of cells to growth factor receptor-, Fc receptor-, or TLR-mediated signaling. Finally, TLT2 ligation potentiates the recruitment of neutrophils to sites of inflammation in vivo. These findings reveal a novel functional role for TLT2 that involves potentiation of neutrophil responses to G protein-coupled receptor signaling. Thus, TLT2 appears to play an important role in enhancing the innate immune response via a novel molecular mechanism.
AB - Receptors encoded within the Trem locus have been shown to play an important role in modulating the cellular response to pattern recognition receptor signaling. TREM-like transcript 2 (TLT2) is a member of the Trem locus that is conserved in mouse and human. TLT2 exhibits a unique expression pattern in that it is expressed on cells of the myeloid and lymphoid lineage, suggesting that it plays a role in both innate and adaptive immunity. In this work, studies reveal that TLT2 plays an important role in potentiating neutrophil antibacterial activity and chemotaxis. TLT2 ligation enhances the neutrophil response to the formylated peptide FMLF, leading to increased reactive oxygen species production, degranulation, and chemotaxis. Moreover, TLT2 has the ability to specifically potentiate neutrophil activation and chemotaxis in response to a range of agonists that bind to G protein-coupled receptors, as it does not potentiate the response of cells to growth factor receptor-, Fc receptor-, or TLR-mediated signaling. Finally, TLT2 ligation potentiates the recruitment of neutrophils to sites of inflammation in vivo. These findings reveal a novel functional role for TLT2 that involves potentiation of neutrophil responses to G protein-coupled receptor signaling. Thus, TLT2 appears to play an important role in enhancing the innate immune response via a novel molecular mechanism.
UR - http://www.scopus.com/inward/record.url?scp=80052649294&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1100534
DO - 10.4049/jimmunol.1100534
M3 - Article
C2 - 21804015
AN - SCOPUS:80052649294
SN - 0022-1767
VL - 187
SP - 2346
EP - 2355
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -