Chicken-Specific Kinome Analysis of Early Host Immune Signaling Pathways in the Cecum of Newly Hatched Chickens Infected With Salmonella enterica Serovar Enteritidis

Abstract

Poultry is a major source of human foodborne illness caused by broad host range Salmonella serovars (paratyphoid), and developing cost-effective, pre-harvest interventions to reduce these pathogens would be valuable to the industry and consumer. Host responses to infectious agents are often regulated through phosphorylation. However, proteomic mechanisms of Salmonella acute infection biology and host responses to the bacteria have been limited concentrating predominately on the genomic responses of the host to infection. Our recent development of chicken-specific peptide arrays for kinome analysis of host phosphorylation-based cellular signaling responses provided us with the opportunity to develop a more detailed understanding of the early (4-24 h post-infection) host-pathogen interactions during the initial colonization of the cecum by Salmonella. Using the chicken-specific kinomic immune peptide array, biological pathway analysis showed infection with S. Enteritidis increased signaling related to the innate immune response, relative to the non-infected control ceca. Notably, the acute innate immune signaling pathways were characterized by increased peptide phosphorylation (activation) of the Toll-like receptor and NOD-like receptor signaling pathways, the activation of the chemokine signaling pathway, and the activation of the apoptosis signaling pathways. In addition, Salmonella infection induced a dramatic alteration in the phosphorylation events of the JAK-STAT signaling pathway. Lastly, there is also significant activation of the T cell receptor signaling pathway demonstrating the initiation of the acquired immune response to Salmonella infection. Based on the individual phosphorylation events altered by the early Salmonella infection of the cecum, certain conclusions can be drawn: (1) Salmonella was recognized by both TLR and NOD receptors that initiated the innate immune response; (2) activation of the PPRs induced the production of chemokines CXCLi2 (IL-8) and cytokines IL-2, IL-6, IFN-α, and IFN-γ; (3) Salmonella infection targeted the JAK-STAT pathway as a means of evading the host response by targeting the dephosphorylation of JAK1 and TYK2 and STAT1,2,3,4, and 6; (4) apoptosis appears to be a host defense mechanism where the infection with Salmonella induced both the intrinsic and extrinsic apoptotic pathways; and (5) the T cell receptor signaling pathway activates the AP-1 and NF-κB transcription factor cascades, but not NFAT.

Mapping the Protein Kinome: Current Strategy and Future Direction

“…The species-specific kinome peptide arrays were designed for bovine species to study Salmonella within the peripheral lymph nodes [ 44 ]. The chicken-specific peptide arrays were used to analyze the kinome alteration of host responses to Salmonella [ 45 ]. These studies have contributed to the development of cost-effective, pre-harvest intervention strategies to prevent pathogen infection.…”

Phenotype Alterations in the Cecal Ecosystem Involved in the Asymptomatic Intestinal Persistence of Paratyphoid Salmonella in Chickens

“…Disease resistance is the host defense strategy grounded on the immune response's capacity to detect and eliminate pathogens, i.e., host immunity [48][49][50]. The initial phase of the chicken cecum to Salmonella infection is manifested by the absence of clinical disease and functions to control pathogen invasion and reduce or eliminate the invading pathogen [48]. Specifically, Salmonella infection: (1) activated both Toll-like receptor (TLR) and Nod-like receptor (NLR) signaling pathways to initiate an innate immune response; (2) induced the production of chemokines CXCLi2 (IL-8) and cytokines IL-2, IL-6, IFN-α, and IFN-γ;…”

“…(3) induced the phosphorylation of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway that initiates innate immunity and coordinates adaptive immune mechanisms; (4) triggered both the intrinsic and extrinsic apoptotic pathways; and (5) activated the T cell receptor signaling pathway through the AP-1 and NF-κB transcription factor cascades [48].…”

“…Disease resistance is the host defense strategy grounded on the immune response’s capacity to detect and eliminate pathogens, i.e., host immunity [ 48 , 49 , 50 ]. The initial phase of the chicken cecum to Salmonella infection is manifested by the absence of clinical disease and functions to control pathogen invasion and reduce or eliminate the invading pathogen [ 48 ].…”

“…Disease resistance is the host defense strategy grounded on the immune response’s capacity to detect and eliminate pathogens, i.e., host immunity [ 48 , 49 , 50 ]. The initial phase of the chicken cecum to Salmonella infection is manifested by the absence of clinical disease and functions to control pathogen invasion and reduce or eliminate the invading pathogen [ 48 ]. Specifically, Salmonella infection: (1) activated both Toll-like receptor (TLR) and Nod-like receptor (NLR) signaling pathways to initiate an innate immune response; (2) induced the production of chemokines CXCLi2 (IL-8) and cytokines IL-2, IL-6, IFN-α, and IFN-γ; (3) induced the phosphorylation of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway that initiates innate immunity and coordinates adaptive immune mechanisms; (4) triggered both the intrinsic and extrinsic apoptotic pathways; and (5) activated the T cell receptor signaling pathway through the AP-1 and NF-κB transcription factor cascades [ 48 ].…”