Effects of immunosuppression on tracheal mucosal responses after infection with Mycoplasma gallisepticum in vaccinated and unvaccinated chickens

Sathya N. Kulappu Arachchige, Anna Kanci Condello, Amir H. Noormohammadi, Kelly A. Tivendale, Glenn F. Browning, Nadeeka K. Wawegama

Introduction Vaccination is the most common method used to control infection caused by Mycoplasma gallisepticum in chickens. However, concurrent immunosuppression may compromise vaccine efficacy. Methods This study investigated the effect of immunosuppression induced by either chicken anaemia virus (CAV) or infectious bursal disease virus (IBDV), administered prior to or following vaccination with the M. gallisepticum live vaccine strain ts-304 (Vaxsafe MG304), on tracheal host responses to subsequent challenge with virulent M. gallisepticum . Tracheal responses were assessed by genome-wide transcriptional profiling in these groups and compared across unvaccinated-unchallenged, unvaccinated-challenged, vaccinated-unchallenged and vaccinated-challenged groups that had not been exposed to CAV or IBDV. Results Immunosuppression resulted in significant differences in tracheal transcriptional responses compared to immunocompetent groups, irrespective of the timing of infection with CAV or IBDV. Differences in transcription were more pronounced in the IBDV-infected groups than the CAV-infected groups. Functional interrogation of differentially transcribed genes revealed adverse effects of M. gallisepticum on extracellular and intracellular signalling, cell communication, cellular actin dynamics, formation of the cellular cytoskeleton, and cellular metabolic pathways in the tracheal mucosa of immunosuppressed groups. In addition, there were indications of down-regulation of both innate and adaptive immune responses, including cytokine signalling, antigen processing presentation, and immune cell receptor signalling in the immunosuppressed groups. Specifically, findings indicated that infection with CAV impaired pro-inflammatory and adaptive T-cell responses in the tracheal mucosa. Conclusions The findings implied that the primary immune response induced post-vaccination and the secondary immune response induced post-challenge with virulent M. gallisepticum were both affected by infection with these two viruses. Coupled with previous observations of reduced antibody titres against M. gallisepticum , and increased rates of recovery of virulent M. gallisepticum in both CAV- and IBDV-infected groups, the significant transcriptional changes detected in the current study highlighted the roles of both cell-mediated (CMI) and humoral immunity (HI) in vaccine-induced protection, as CAV mainly affects CMI and IBDV mainly affects HI. These findings will assist in identifying the mechanisms underlying the reduced efficacy of live attenuated mycoplasma vaccines in immunosuppressed animals.