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

  • ️Tue Jan 01 2008

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

Xueshui Guo et al. Vet Immunol Immunopathol. 2008.

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.

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Figures

Fig. 1
Fig. 1

A flowchart schematically shows the microarray experiment design. C1-24, pooled samples from age-matched control chickens; T, IBV-Mass immunized chickens; the numbers indicated the day after the primary immunization. Total RNA from each group was used to compare with RNA from other four groups as indicated by the lines between the groups. The arrowhead pointed samples were labeled with Cy5 and hybridized with the samples on the other end of the lines, which were labeled with Cy3. Four different RNA samples were used for the four different hybridizations at each time point with the chicken 13 k cDNA microarray slides (FHCRC, Seattle, WA).

Fig. 2
Fig. 2

Expression profiles of local innate immunity after attenuated IBV-Mass immunizations. Rows are individual genes, and columns are the measurement taken at different time points. Colors represent the relative gene expression level. Green indicates an expression below the mean value for the gene, black indicates an expression near the mean, and red indicates an expression above the mean. log2 fold changes of genes used in clustering analysis are provided in Supplementary Table 3. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.)

Fig. 3
Fig. 3

Expression profiles of local adaptive immunity after attenuated IBV-Mass immunizations. Rows are individual genes, and columns are measurement taken at different time points. Colors represent the relative gene expression level. Green indicates an expression below the mean value for the gene, black indicates an expression near the mean, and red indicates an expression above the mean. log2 fold changes of genes used in clustering analysis are provided in Supplementary Table 3. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.)

Fig. 4
Fig. 4

A proposed model on the molecular kinetics of mucosal immunity following local immunizations of IBV-Mass. IBV antigen is firstly recognized by two independent innate mechanisms including TLR and RIG-1. Cytokines such as IL-1β and IFNs activated by the innate pathways regulated the activation of T cells and induced cells to an anti-viral state. In addition, a number of other innate responses are also induced, including phagocytosis, complement, inflammation, cell death, and antigen presentation, which created an ideal microenvironment for T-cell activation and served as a bridging factor for connecting the local innate and adaptive immune systems. Once the T cells are activated, two branches of adaptive immune responses are initiated with CTLs being activated initially, followed by humoral immunity. CTLs, together with parts of the innate immunity, are responsible for the virus clearance from the local infection sites. Local IgG is the only and dominant arm of local secondary immunity against subsequent virus exposure.

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