Transcriptional Profiling of the Chicken Tracheal Response to Virulent Mycoplasma gallisepticum Strain R _low

Abstract

, the primary etiologic agent of chronic respiratory disease (CRD) in poultry, leads to prolonged recruitment and activation of inflammatory cells in the respiratory mucosa. This is consistent with the current model of immune dysregulation that ostensibly allows the organism to evade clearance mechanisms and establish chronic infection. To date, studies using quantitative reverse transcription-PCR (qRT-PCR) and microarrays have shown a significant transient upregulation of cytokines and chemokines from tracheal epithelial cells (TECs) and tracheal tissue in response to virulent strain R that contributes to the infiltration of inflammatory cells into the tracheal mucosa. To expand upon these experiments, RNA was isolated from tracheas of 20 chickens infected with R and 20 mock-infected animals at days 1, 3, 5, and 7 postinoculation, and samples were analyzed for differential gene expression using Illumina RNA sequencing. A rapid host response was observed 24 h postinfection, with over 2,500 significantly differentially expressed genes on day 3, the peak of infection. Many of these genes have immune-related functions involved in signaling pathways, including Toll-like receptor (TLR), mitogen-activated protein kinase, Jak-STAT, and the nucleotide oligomerization domain-like receptor pathways. Of interest was the increased expression of numerous cell surface receptors, including TLR4 and TLR15, which may contribute to the production of cytokines. Metabolic pathways were also activated on days 1 and 3 postinfection, ostensibly due to epithelial cell distress that occurs upon infection. Early perturbations in tissue-wide gene expression, as observed here, may underpin a profound immune dysregulation, setting the stage for disease manifestations characteristic of infection.

Immunologic Pathways in Protective versus Maladaptive Host Responses to Attenuated and Pathogenic Strains of Mycoplasma gallisepticum

“…Previous transcriptomic analysis conducted in our laboratory indicated a massive and dynamic host tracheal response associated with virulent R low infection over 7 days, highlighting the immunological, metabolic, and stress-and injury-related genes and pathways which may contribute to the exaggerated and dysregulated host response (10). To better understand differences between virulent and nonimmunopathologic host responses, we conducted a 2-day infection study followed by RNA sequencing (RNA-Seq) to assess the host transcriptional differences in genes and pathways leading to either a maladaptive or beneficial immune response to M. gallisepticum (25). Responses against intratracheally administered GT5 and Mg7 LAVs were compared to responses against R low at early time points postinfection.…”

Variable Lipoprotein Hemagglutinin A Gene ( vlhA ) Expression in Variant Mycoplasmagallisepticum Strains In Vivo

“…The vaccine strains Mg7 and GT5 show a significant reduction in virulence (6,16) in the host and do not show the same initial progression of vlhA gene expression as that shown by wild-type virulent R low . Additionally, M. gallisepticum GT5 and Mg7 do not cause the same host cell stress response or immune dysregulation (J. Beaudet, unpublished data) that is observed in chickens experimentally challenged with virulent wild-type R low (18). It is possible that since the trachea is not being disrupted or damaged by the vaccine strains, the vlhA genes are not forced to change in response.…”

Mycoplasma gallisepticum Infection Impaired the Structural Integrity and Immune Function of Bursa of Fabricius in Chicken: Implication of Oxidative Stress and Apoptosis

“…Previous studies demonstrated that MG is the primary cause of chronic respiratory disease in chickens and infectious sinusitis in turkeys, characterized by nasal discharge, sneezing, and coughing (2,3). Researchers reported that MG-infection causes significant economic losses to the poultry industry including the reduction in egg production, hatchability, and low meat quality (4)(5)(6). MGinfection induces respiratory distress, profound inflammatory response in mucosal tissues and immune dysregulation in chickens (4).…”

“…Researchers reported that MG-infection causes significant economic losses to the poultry industry including the reduction in egg production, hatchability, and low meat quality (4)(5)(6). MGinfection induces respiratory distress, profound inflammatory response in mucosal tissues and immune dysregulation in chickens (4). Moreover, the property of cytoadherence of MG produced additional virulence factors including superoxide radicals leading to immune dysregulation (4,7).…”

“…MGinfection induces respiratory distress, profound inflammatory response in mucosal tissues and immune dysregulation in chickens (4). Moreover, the property of cytoadherence of MG produced additional virulence factors including superoxide radicals leading to immune dysregulation (4,7). However, the mechanism underlying immune dysregulation induced by MGinfection is still unclear.…”