Differential Response of the Chicken Trachea to Chronic Infection with Virulent Mycoplasma gallisepticum Strain Ap3AS and Vaxsafe MG (Strain ts-304): a Transcriptional Profile

Abstract

Mycoplasma gallisepticum is the primary etiological agent of chronic respiratory disease in chickens. Live attenuated vaccines are most commonly used in the field to control the disease, but current vaccines have some limitations. Vaxsafe MG (strain ts-304) is a new vaccine candidate that is efficacious at a lower dose than the current commercial vaccine strain ts-11, from which it is derived. In this study, the transcriptional profiles of the trachea of unvaccinated chickens and chickens vaccinated with strain ts-304 were compared 2 weeks after challenge with M. gallisepticum strain Ap3AS during the chronic stage of infection. After challenge, genes, gene ontologies, pathways, and protein classes involved in inflammation, cytokine production and signaling, and cell proliferation were upregulated, while those involved in formation and motor movement of cilia, formation of intercellular junctional complexes, and formation of the cytoskeleton were downregulated in the unvaccinated birds compared to the vaccinated birds, reflecting immune dysregulation and the pathological changes induced in the trachea by infection with M. gallisepticum. Vaccination appears to protect the structural and functional integrity of the tracheal mucosa 2 weeks after infection with M. gallisepticum.

Transcriptomic Analysis of Long-Term Protective Immunity Induced by Vaccination With Mycoplasma gallisepticum Strain ts-304

“…This study also identified differences and similarities in the immunopathological changes seen in this study in the tracheal mucosa of mature birds after challenge with M. gallisepticum and those seen in young birds after challenge in a previous study ( 28 ). These similarities and differences are outlined in Table 6 .…”

“…These similarities and differences are outlined in Table 6 . Notably, the inflammatory response seen in the tracheal mucosa was less severe in birds infected with M. gallisepticum at 60 weeks of age than that seen after infection at 7 weeks of age ( 28 ) ( Table 6 ). An earlier study that investigated the age-related differences in the immune response to infection with M. gallisepticum in chickens between 1 and 6 weeks of age found that the lesions were most severe in the younger birds ( 59 ), suggesting that older birds are less susceptible to disease caused by infection with M. gallisepticum .…”

“…Previous studies examining the efficacy and safety of mycoplasma vaccines have focused on assessment of gross and histopathological lesions and evaluation of the adaptive immune response by measuring the antibody response in vaccinated birds after challenge ( 11 , 16 , 22 – 24 , 44 , 45 ). Only a few, recent studies have investigated the genes and/or pathways underlying protection against disease by examining the host responses to vaccination and/or infection with M. gallisepticum ( 26 – 28 ) in order to further understand the pathogenetic processes underlying the pathology and the immune responses to infection with the aim of improving the vaccine development process. While the study reported here demonstrated that chickens vaccinated with ts-304 were protected against the adverse effects on the tracheal mucosa after infection with virulent M. gallisepticum , we were unable to detect genes or pathways that were involved in this protection, as there were no detectable differences in gene transcription between the two vaccinated groups (vaccinated-and-challenged and vaccinated-only) and the uninfected, negative control group, suggesting that within 2 weeks of infection the immunity provided by the vaccine facilitated the resumption of the normal structural and functional capacity of the tracheal mucosa.…”

“…Differentially transcribed genes were further analyzed by gene ontology (GO) enrichment using the topGO version 2.36.0 ( 40 ) R/Bioconductor package as previously described ( 28 ). Briefly, a G. gallus GO universe was constructed using GO-IDs linked to each protein-coding gene of G. gallus , extracted using the biomaRt annotation tool version 2.40.0 ( 41 ), to identify molecular functions (MFs), biological processes (BPs), and cellular components (CCs) enriched with up- or down-regulated genes at a FDR of < 0.01.…”

Mycoplasma hyopneumoniae J elicits an antioxidant response and decreases the expression of ciliary genes in infected swine epithelial cells

“…In addition, genes necessary for axonemal dynein assembly (DYX1C1) 46 , genes related to ciliogenesis (CEP162, DCDC2, MACF1, IFT57) [47][48][49][50] , ciliary polarization (INTU) 51 , ciliary beating (MYO1D) 52 and several others in which the mutation or knockout is associated with ciliopathies (LRRC6, MNS1, AK7) [53][54][55] were down-regulated in the infected cells (Table 4). Interestingly, in line with our results, a recent study compared the transcriptional response of unvaccinated and vaccinated chicken infected with M. gallisepticum and the authors identified enrichment of GO terms in downregulated genes related to cilia and cytoskeleton in unvaccinated animals 56 . Protein functions encoded by the top down-regulated genes were involved in microtubule assembly and stability, axonemal dynein complex assembly, and formation and motor movement of cilia, indicating that at least in one Mycoplasma species the ciliary damage caused by infection could be also explained by the down-regulation of genes involved in the ciliary function.…”