Marek's disease virus-induced transient cecal tonsil atrophy

Marek's disease (MD) is a lymphoproliferative disease of domestic chickens that is caused by a highly cell-associated oncogenic alpha-herpesvirus, Marek's disease virus (MDV). MDV replicates in chicken lymphocytes and establishes a latent infection within CD4+ T cells. MD is characterized by bursal and thymic atrophy and rapid onset of T cell lymphomas that infiltrate lymphoid tissues, visceral organs, and peripheral nerves with severe clinical symptoms that include transient paralysis, anemia, weight loss, and neurologic disorders. The cecal tonsils (CT) are considered the largest lymphoid aggregates of avian gut-associated lymphoid tissue (GALT). Along with Peyer's patches, CT elicits protective immune responses against bacterial and viral pathogens in the intestinal tract of avian species. In this study we investigated the effect of MDV infection on CT structural changes and cytokine gene expression in two MD-susceptible and resistant chicken lines. The histopathologic analysis revealed that MDV causes the loss of germinal follicular centers within the CT of the resistant line while inducing a severe, near-total lymphoid depletion in the susceptible line during cytolytic infection. The lymphoid depletion, however, recovered approximately 2 wk postinfection but the loss of germinal centers persisted during the latent phase of infection in both lines. The atrophy of this important GALT was transient and there were no visible differences between the CT of the infected and control birds of either line by 21 days postinfection. Of the genes tested, IFN-beta and IFN-gamma were up regulated in the CT of both infected lines during lytic infection. The expression levels of both genes were much higher in the susceptible line than in the resistant line. A similar pattern of expression was observed for IL-6, IL-10, IL-13, and iNOS. IL-12 was up regulated in the CT of birds of the susceptible line during all three phases of infection. An over expression of IL-18 was also observed in CT of the susceptible line during lytic and latent phases of infection. IL-8 was the only cytokine expressed at higher levels in the CT of the resistant line during the lytic and reactivation phases of infection. The histopathologic observations and gene expression profiling are further discussed.