|Kogut, Michael - Mike|
|He, Louis - Haiqi|
Submitted to: Veterinary Immunology International Symposium
Publication Type: Abstract only
Publication Acceptance Date: 5/28/2004
Publication Date: 7/25/2004
Citation: Kogut, M.H., Iqbal, M., He, H., Philbin, V., Kaiser, P., Smith, A. 2004. Heterophil toll-like receptors: Recognition, signaling and functional activation [abstract]. 7th International Veterinary Immunology Symposium. p. 395. 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), poly (I:C), the guanosine analog, loxoribine, and the synthetic oligodeoxynucleotide, CpG-ODN all increased phagocytosis and directly induced 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 a differential increase in p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase 1/2 (ERK 1/2) activation. Treatment of the cells with either SB203580, a specific p38 MAPK inhibitor, or U0126, a specific inhibitor of ERK 1/2, 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. 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. 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.