Molecular mechanisms of primary and secondary mucosal immunity using avian infectious bronchitis virus as a model system.

Department of Biology and Microbiology, South Dakota State University, Brookings, SD 57007, USA.
Veterinary Immunology and Immunopathology (Impact Factor: 1.88). 03/2008; 121(3-4):332-43. DOI: 10.1016/j.vetimm.2007.09.016
Source: PubMed

ABSTRACT Although mucosal immune responses are critical for protection of hosts from clinical illness and even mortality caused by mucosal pathogens, the molecular mechanism of mucosal immunity, which is independent of systemic immunity, remains elusive. To explore the mechanistic basis of mucosal protective immunity, gene transcriptional profiling in mucosal tissues was evaluated after the primary and secondary immunization of animals with an attenuated avian infectious bronchitis virus (IBV), a prototype of Coronavirus and a well-characterized mucosal pathogen. Results showed that a number of innate immune factors including toll-like receptors (TLRs), retinoic-acid-inducible gene-1 (RIG-1), type I interferons (IFNs), complements, and interleukin-1 beta (IL-1beta) were activated locally after the primary immunization. This was accompanied or immediately followed by a potent Th1 adaptive immunity as evidenced by the activation of T-cell signaling molecules, surface markers, and effector molecules. A strong humoral immune response as supported by the significantly up-regulated immunoglobulin (Ig) gamma chain was observed in the absence of innate, Th1 adaptive immunity, or IgA up-regulation after the secondary immunization, indicating that the local memory response is dominated by IgG. Overall, the results provided the first detailed kinetics on the molecular basis underlying the development of primary and secondary mucosal immunity. The key molecular signatures identified may provide new opportunities for improved prophylactic and therapeutic strategies to combat mucosal infections.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract The antibody and cellular immune responses against infectious bronchitis virus (IBV) were evaluated at mucosal sites of chickens after immunization with various doses of an attenuated vaccine at 1 day of age. The correlation of these immune responses with protection of tracheal tissues was evaluated after experimental infection of these birds. Significantly reduced tracheal pathologic effects, measured according to ciliostasis and histology lesions, and reduced viral load were observed only in the full-dose vaccinated group at 5 days post-infection (dpi), while incomplete protection was observed for the subdose vaccinated groups. Moreover, birds of vaccinated groups, especially with full dose, developed higher levels of lachrymal IBV-specific IgG and IgA and increased the expression of cell-mediated immunity (CMI) genes, such as gamma interferon (IFNγ), CD8+ T cell marker, and granzyme homolog A more rapidly. In addition, these humoral and cellular immune responses evaluated at mucosal sites correlated significantly with tracheal protection against homologous IBV challenge in a vaccine dose-dependent manner. The results indicate that IgG, IgA and CD8+ T cell responses developed at mucosal sites after IBV vaccination of day-old chicks, could be taken as good correlates of protection against this virus.
    Viral immunology 07/2013; · 1.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Infectious bronchitis virus (IBV) replicates in the epithelial cells of trachea and lungs of chicken, however the mechanism of generation of innate immune response against IBV infection in these tissues has not been fully characterized. Our objective was to study innate responses induced early following IBV infection in chickens. Initiation of the transcription of selected innate immune genes such as TLR3, TLR7, MyD88, IL-1β and IFN-β, as well as recruitment of macrophages, were evident following an initial down regulation of some of the observed genes (TLR3, IL-1β, and IFN-γ) in trachea and lung. This initial down-regulation followed by the induction of innate immune response to IBV infection appears to be inadequate for the control of IBV genome accumulation and consequent histopathological changes in these tissues. Potential induction of innate immunity before infection occurs may be necessary to reduce the consequences since vaccine induced immunity is slow to develop.
    Virology 01/2014; s 450–451:114–121. · 3.35 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We have previously reported that inhibition of phosphatidylinositol 3-kinase (PI3K) reduces porcine reproductive and respiratory syndrome (PRRSV) replication. Here, we further investigate the mechanism by which PI3K inhibition affects virus replication and the role of Akt1 kinase in virus replication. We found that PI3K inhibition reduced viral gene transcription by approximately 1.5-fold. Accordingly, viral protein synthesis was significantly reduced by PI3K inhibition. Interestingly, cells overexpressing the dominant negative mutant Akt1 exhibited a significant reduction in viral gene transcription compared to cells overexpressing the constitutively active Akt1. Viral protein synthesis was also enhanced in cells overexpressing the constitutively active Akt1. Overall, our data show that both PI3K and Akt1 play a role in viral gene expression, leading to an increase in virus replication.
    Archives of Virology 02/2014; · 2.03 Impact Factor