Protein tyrosine kinase and mitogen-activated protein kinase signalling pathways contribute to differences in heterophil-mediated innate immune responsiveness between two lines of broilers

Abstract

Protein tyrosine phosphorylation mediates signal transduction of cellular processes with protein tyrosine kinases (PTKs) regulating virtually all signalling events. The mitogen-activated protein kinase (MAPK) super-family consists of three conserved pathways that convert receptor activation into cellular functions: extracellular response kinases (ERK), c-Jun N-terminal kinases (JNK) and p38. Previously conducted studies using two chicken lines (A and B) show line A heterophils are functionally more responsive and produce a differential cytokine/chemokine profile compared with line B, which also translates to increased resistance to bacterial challenges. Therefore, we hypothesize the differences between the lines result from distinctive signalling cascades that mediate heterophil function. Heterophils from lines A and B were isolated from 1-day-old chickens and total phosphorylated PTK and p38, JNK, ERK, and transcription factor (activator protein 1 (AP-1) and nuclear factor kappa B (NF-kB)) protein levels quantified following interaction with Salmonella Enteritidis (SE). Control and SE-treated heterophils from line A had greater (P50.05) PTK phosphorylation compared to line B with increased (P50.05) activation of p38. Conversely, line B heterophils activated JNK (P50.05). There were no differences in ERK between control and activated heterophils for either line. Defined signalling inhibitors were used to show specificity. The AP-1 and NF-kB transcription factor families were also examined, and c-Jun and p50, respectively, were the only members different between the lines and both were up-regulated in line A compared with line B. These data indicate that increased responsiveness of line A heterophils is mediated, largely, by an increased ability to activate PTKs, the p38 MAPK pathway and specific transcription factors, all of which directly affect the innate immune response.

Comparative analysis of the caecal tonsil transcriptome in two chicken lines experimentally infected with Salmonella Enteritidis

“…However, one of the four common BP GO terms may be directly related to the Salmonella infection process: the transmembrane receptor protein tyrosine kinase signalling pathway (GO:0007169), which is enriched in low carriers in both lines. Several studies have shown that the activation of protein tyrosine kinases and other specific transcription factors directly affects the innate immune response during SE infection [ 5 , 25 ]. Therefore, the transcriptional up-regulation of this pathway may be one of the mechanisms by which the animals from both lines control the infection.…”

Comparative analysis of the caecal tonsil transcriptome in two hen lines experimentally infected withSalmonellaEnteritidis

“…However, one of the four common BP GO terms may be directly related to the Salmonella infection process: the transmembrane receptor protein tyrosine kinase signalling pathway (GO:0007169), which is enriched in low carriers in both lines. Several studies have shown that the activation of protein tyrosine kinases and other specific transcription factors directly affects the innate immune response during SE infection [5,35]. Therefore, the transcriptional up-regulation of this pathway may be one of the mechanisms by which the animals from both lines control the infection.…”

Differential Levels of Cecal Colonization by Salmonella Enteritidis in Chickens Triggers Distinct Immune Kinome Profiles

“…Another study in chickens showed that increased resistance against S . Enteritidis organ invasion is associated with elevated production of p38 and decreased production of JNK ( 32 ) while increased production of p38, JNK, and ERK are all influential in determining the level of resistance in turkeys ( 33 ). Involvement of the MAPK signaling pathway extends beyond mere immunological responses by the host.…”