|Kogut, Michael - Mike|
|He, Louis - Haiqi|
Submitted to: Avian Immunology Research Group Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 5/3/2004
Publication Date: 9/4/2004
Citation: Kogut, M.H., Iqbal, M., He, H., Philbin, V., Kaiser, P., Smith, A. 2004. Expression and function of toll-like receptors in chicken heterophils [abstract]. 8th Avian Immunology Research Group Meeting. p. 23. Interpretive Summary:
Technical Abstract: For the first time, we have investigated the mRNA expression of a panel of Toll-like receptors (TLR) and their functions in chicken heterophils. Heterophils constitutively expressed TLR1/6, TLR2 type 1, TLR type 2, TLR3, TLR4, TLR5, and TLR7. Furthermore, among the various TLR agonists, flagellin (from Salmonella typhimuirum), ultra-pure lipopolysaccharide (from Salmonella minnesota), heat-killed Listeria monocytogenes, poly (I:C), and the guanosine analog, loxoribine, all induced the typical antimicrobial functions, an oxidative burst and a degranulation response. The only exception was the synthetic bacterial lipoprotein Pam3CSK4 (palmitoyl-3-cysteine-serine-lysine-4) that induced degranulation, but no oxidative burst. Stimulation of heterophils with each specific TLR agonist led to p38 mitogen-activated protein kinase (MAPK) activation. Treatment of the cells with SB203580, a specific p38 MAPK inhibitor, almost completely attenuated TLR-agonist induced degranulation and oxidative burst. Interestingly, the c-Jun N-terminal kinase (JNK) inhibitor (SP600125) partially attenuated (30-60%) TLR-induced heterophil degranulation, but had no effect on the TLR-induced oxidative burst. However, U0126, a specific inhibitor of extracellular signal-regulated kinase (ERK) had no effect on either TLR agonist-induced antimicrobial functional activity. The broad TLR expression profile in heterophils strongly reflects their principal role as first line effector cells in avian host defense against bacterial, viral, and fungal infections. Our results suggest that triggering of heterophil TLR3 (poly(I:C) and TLR7 (loxoribine) systems represent a potentially important role against viral infections by the release of antiviral secretory granules. The results are also indicative of the differential stimulation of signaling pathways that regulate the oxygen-dependent and 'independent antimicrobial defense mechanisms of avian heterophils.