Author
Heidari, Mohammad | |
FITZGERALD, SCOTT - Michigan State University | |
Zhang, Huanmin |
Submitted to: Avian Diseases
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 2/16/2015 Publication Date: N/A Citation: N/A Interpretive Summary: Toll-like receptors (TLRs) are pattern recognition receptors expressed on the surfaces of certain cells that recognize conserved pathogen-associated molecular patterns and trigger pro-inflammatory cytokine production such as interleukins and interferons. Among the innate defense mechanisms, TLRs play an important role in recognition of pathogens and elicitation of innate and adaptive immune responses against viruses and bacteria. In this study, we examined the effect of Marek’s disease virus (MDV) infection on TRL expression pattern in the cecal tonsils (CT) of MDV-infected chickens. Real-Time PCR gene expression profiling revealed that of the ten TLRs tested, TLR 2A, TLR3, TLR5, and TLR15 displayed significant differential expression pattern at different time points post inoculation. Immunohistochemical analysis showed a severe depletion of B and T cells in the CT of both lines at 5 dpi, which recovered by 21dpi. A significant infiltration of macrophages were observed after the depletion of B and T cells in the infected birds of both lines that could account for the differential TLR gene expression in the infected birds. The data presented provides further insight into mechanism of MDV pathogenesis and tissue specific immunological responses to viral infection. Technical Abstract: Marek’s disease (MD) is a lymphoproliferative disease of domestic chickens that is caused by a highly cell-associated oncogenic '-herpesvirus, Marek’s disease virus (MDV). MDV replicates in chicken lymphocytes and establishes a latent infection within CD4+ T cells. Clinical signs of MD include depression, crippling, weight loss, bursal/thymic atrophy, neurological disorders and rapid onset of T cell lymphomas that infiltrate lymphoid tissues, visceral organs, and peripheral nerves. 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 Toll-like receptor (TLR) gene expression in CT of two MD-susceptible (7-2) and resistant (6-3) chicken lines. Real-Time PCR gene expression profiling revealed that of the ten TLRs tested, TLR 2A, TLR3, TLR5, and TLR15 displayed significant differential expression pattern at different time points post inoculation. TLR2A was highly expressed at 21 days post infection (dpi) in line 6-3 and 14 dpi in line 7-2. Its expression, however, was suppressed at 5 and 14 dpi in the susceptible line. TLR3 was down regulated at all three time points in the resistant line. Its expression, however, was highly up regulated in the susceptible line at 21 dpi. The expression levels of TLR5 in CT of the infected birds of 6-3 were lower than those of the control birds at 5 and 21 dpi. It was, however, up regulated at 14 dpi. Despite the initial down regulation of this receptor in the infected susceptible line, its transcriptional activity was significantly higher than those of the control birds at 14 dpi. TLR15, a chicken specific gene with no ortholog in other species, was highly expressed in line 6-3 at 21 dpi and in line 7-2 at 14 dpi. Its expression was lower than those of the control birds of line 7-2 at 5 and 21 dpi. The expression levels of the remaining six genes were minimally affected by MDV infection in either line. Immunohistochemical analysis showed a severe depletion of B and CD4+ T cells in the CT of susceptible line at 5 dpi, which recovered by 21dpi. The destruction of B and T cells in the CT of the resistant line was minimal at 5 dpi, which also recovered by 21 dpi. A significant infiltration of macrophages were observed after the depletion of B and T cells in the infected birds of both lines that could account for the differential TLR gene expression in the infected birds. The data presented provides further insight into mechanism of MDV pathogenesis and tissue specific immunological responses to viral infection. |