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https://www.arca.fiocruz.br/handle/icict/67524
BCG INFECTION DOSE GUIDES DENDRITIC CELL MIGRATION AND T CELL PRIMING IN THE DRAINING LYMPH NODE
Author
Affilliation
Karolinska Institutet. Department of Microbiology, Tumor and Cell Biology. Stockholm, Sweden.
Karolinska Institutet. Department of Microbiology, Tumor and Cell Biology. Stockholm, Sweden.
Karolinska Institutet. Department of Microbiology, Tumor and Cell Biology. Stockholm, Sweden.
Karolinska Institutet. Department of Microbiology, Tumor and Cell Biology. Stockholm, Sweden / Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Karolinska Institutet. Department of Microbiology, Tumor and Cell Biology. Stockholm, Sweden.
Karolinska Institutet. Department of Microbiology, Tumor and Cell Biology. Stockholm, Sweden.
Karolinska Institutet. Department of Microbiology, Tumor and Cell Biology. Stockholm, Sweden.
Karolinska Institutet. Department of Microbiology, Tumor and Cell Biology. Stockholm, Sweden / Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Karolinska Institutet. Department of Microbiology, Tumor and Cell Biology. Stockholm, Sweden.
Abstract
In contrast to delayed-type hypersensitivity (DTH) and other hallmark reactions of cell-mediated immunity that correlate with vaccine-mediated protection against Mycobacterium tuberculosis, the contribution of vaccine dose on responses that emerge early after infection in the skin with Bacille Calmette–Guérin (BCG) is not well understood. We used a mouse model of BCG skin infection to study the effect of BCG dose on the relocation of skin Dendritic cells (DCs) to draining lymph node (DLN). Mycobacterium antigen 85B-specific CD4+ P25 T cell-receptor transgenic (P25 TCRTg) cells were used to probe priming to BCG in DLN. DC migration and T cell priming were studied across BCG inocula that varied up to 100-fold (10E4 to 10E6 Colony-forming units—CFUs). In line with earlier results in guinea pigs, DTH reaction in our model correlated with BCG dose. Importantly, priming of P25 TCRTg cells in DLN also escalated in a dose-dependent manner, peaking at day 6 after infection. Similar dose-escalation effects were seen for DC migration from infected skin and the accompanying transport of BCG to the
DLN. BCG-triggered upregulation of co-stimulatory molecules on migratory DCs was restricted to the first 24hour after infection and was independent of BCG dose over a 10-fold range (10E5 to 10E6 CFUs). The dose seemed to be a determinant of the number of total skin DCs that move to the DLN. In summary, our results support the use of higher BCG doses to detect robust DC migration and T cell priming.
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