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

Abstract

Mycoplasmas are small bacterial commensals or pathogens that commonly colonize host mucosal tissues and avoid rapid clearance, in part by stimulating inflammatory, immunopathogenic responses. We previously characterized a wide array of transcriptomic perturbations in avian host tracheal mucosae infected with virulent, immunopathologic Mycoplasma gallisepticum; however, mechanisms delineating these from protective responses, such as those induced upon vaccination, have not been thoroughly explored. In this study, host transcriptomic responses to two experimental M. gallisepticum vaccines were assessed during the first 2 days of infection. Relative to virulent infection, host metabolic and immune gene responses to both vaccines were greatly decreased, including early innate immune responses critical to disease development and subsequent adaptive immunity. These data specify host genes and potential mechanisms contributing to maladaptive versus beneficial host responses—information critical for design of vaccines efficacious in both limiting inflammation and enabling pathogen clearance.

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

“…Recovery from infection is correlated with the onset of formation of follicles in the tracheal mucosa, accompanied by B cell infiltration from 3 weeks after infection (20). The absence of lymphocytic aggregations in the tracheal sections in this study suggests that the majority of the infiltrating cells are likely to be T cells and that the severe inflammatory response seen in the chronic phase of the disease is a result of immune dysregulation caused by M. gallisepticum (14)(15)(16)(17)20). There were some indications of B cell migration in the upregulated pathways and GOs (Fig.…”

“…This is the first study to investigate the differences in the transcriptional profiles of the trachea of vaccinated and unvaccinated birds after infection with virulent M. gallisepticum. Previous studies have focused on the acute response to infection with M. gallisepticum (16,17), while this study focused on the tracheal response at a more chronic stage. The similarities and differences between the findings of this study and previous transcriptome studies of acutely infected birds are summarized in Table S2.…”

“…A few studies have explored the role of selected cytokines and chemokines (14), and lipid-associated membrane proteins of M. gallisepticum (15), in the host response. The transcriptional profile of the tracheal response to infection with M. gallisepticum strain R low in unvaccinated chickens has been examined up to 7 days after infection (16,17), and these studies have suggested that the inflammation seen in the trachea is mediated by a panel of proinflammatory cytokines and chemokines via Toll-like receptor (TLR) 2 signaling through an NF-B pathway. However, the regulatory pathways and mechanisms involved in the inflammation seen during the chronic stages of infection have not been explored previously.…”

“…A new vaccine candidate, MG ts-304 (27), has been shown to have a safety profile similar to that of ts-11 but to be efficacious at a lower dose (97). The transcriptional response in the tracheal mucosa has been investigated (17) after exposure to M. gallisepticum vaccine strains GT5 and Mg7 (16) over the first 2 days after exposure, but there have been no previous studies investigating the transcriptional profile in the trachea after challenge with wild-type M. gallisepticum in vaccinated birds.…”

Current status of vaccine research, development, and challenges of vaccines for Mycoplasma gallisepticum

“…Despite extensive research on the pathology of MG, there are several challenges that hinder the triumph of vaccines to prevent MG infection. Among these challenges are immune status of host animals, colonization of MG in host respiratory tract, presence of other respiratory pathogens, phase or antigenic variation that lead to immune escape from the host immune system and transmission of infection in the flocks ( Levisohn et al., 1995 ; Staley and Bonneaud, 2015 ; Beaudet et al., 2017 ; Beaudet et al., 2019 ). Adhesion plays a pivotal role in the colonization and pathogenesis of Mycoplasmas infection ( Henderson and Jensen, 2006 ).…”