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Full restoration of Brucella-infected dendritic cell functionality through V?9V?2 T helper type 1 crosstalk.

ABSTRACT: V?9V?2 T cells play an important role in the immune response to infectious agents but the mechanisms contributing to this immune process remain to be better characterized. Following their activation, V?9V?2 T cells develop cytotoxic activity against infected cells, secrete large amounts of cytokines and influence the function of other effectors of immunity, notably cells playing a key role in the initiation of the adaptive immune response such as dendritic cells. Brucella infection dramatically impairs dendritic cell maturation and their capacity to present antigens to T cells. Herein, we investigated whether V T cells have the ability to restore the full functional capacities of Brucella-infected dendritic cells. Using an in vitro multicellular infection model, we showed that: 1/Brucella-infected dendritic cells activate V?9V?2 T cells through contact-dependent mechanisms, 2/activated V?9V?2 T cells induce full differentiation into IL-12 producing cells of Brucella-infected dendritic cells with functional antigen presentation activity. Furthermore, phosphoantigen-activated V?9V?2 T cells also play a role in triggering the maturation process of dendritic cells already infected for 24 h. This suggests that activated V?9V?2 T cells could be used to modulate the outcome of infectious diseases by promoting an adjuvant effect in dendritic cell-based cellular therapies.

SUBMITTER: Ni M

PROVIDER: S-EPMC3425473 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Full restoration of Brucella-infected dendritic cell functionality through Vγ9Vδ2 T helper type 1 crosstalk.

Ni Ming M Martire Delphine D Scotet Emmanuel E Bonneville Marc M Sanchez Francoise F Lafont Virginie V

PloS one 20120822 8

Vγ9Vδ2 T cells play an important role in the immune response to infectious agents but the mechanisms contributing to this immune process remain to be better characterized. Following their activation, Vγ9Vδ2 T cells develop cytotoxic activity against infected cells, secrete large amounts of cytokines and influence the function of other effectors of immunity, notably cells playing a key role in the initiation of the adaptive immune response such as dendritic cells. Brucella infection dramatically ...[more]

PMID: 22928003

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Project description:Research has been undertaken to understand the host immune response to Brucella canis infection because of the importance of the disease in the public health field and the clinical field. However, the previous mechanisms governing this infection have not been elucidated. Therefore, in vitro models, which mimic the in vivo infection route using a canine epithelial cell line, D17, and a canine macrophage, DH82, were established to determine these mechanisms by performing an analysis of the transcriptomes in the cells. In this study, a coculture model was constructed by using the D17 cell line and DH82 cell line in a transwell plate. Also, a single cell line culture system using DH82 was performed. After the stimulation of the cells in the two different systems infected with B. canis, the gene expression in the macrophages of the two different systems was analyzed by using RNA-sequencing (RNA-seq), and a transcriptomic analysis was performed by using the Ingenuity Pathway Analysis (IPA). Gene expression patterns were analyzed in the DH82 cell line at 2, 12, and 24 h after the stimulation with B. canis. Changes in the upregulated or downregulated genes showing 2-fold or higher were identified at each time point by comparing with the non-stimulated group. Differentially expressed genes (DEGs) between the two culture models were identified by using the IPA program. Generally, the number of genes expressed in the single cell line culture was higher than the number of genes expressed in the coculture model for all-time points. The expression levels of those genes were higher in the single cell line culture (p < 0.05). This analysis indicated that the immune response-related pathways, especially, the dendritic cell maturation, Triggering receptor expression on myeloid cells 1 (TREM1) signaling, and Toll-like receptor (TLR) signaling pathway, were significantly induced in both the culture systems with higher p-values and z-scores. An increase in the expression level of genes related to the pathways was observed over time. All pathways are commonly associated with a manifestation of pro-inflammatory cytokines and early immune responses. However, the Peroxisome proliferator-activation receptor (PPAR) signaling and Liver X Receptor/Retinoid X Receptor (LXR/RXR) signaling associated with lipid metabolism were reduced. These results indicate that early immune responses might be highly activated in B. canis infection. Therefore, these results might suggest clues to reveal the early immune response of the canine to B. canis infection, particularly TLR signaling.

Dataset Information

Full restoration of Brucella-infected dendritic cell functionality through V?9V?2 T helper type 1 crosstalk.

Publications

Full restoration of Brucella-infected dendritic cell functionality through Vγ9Vδ2 T helper type 1 crosstalk.

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