PMID- 38441294 OWN - NLM STAT- MEDLINE DCOM- 20240306 LR - 20240306 IS - 1365-3083 (Electronic) IS - 0300-9475 (Linking) VI - 99 IP - 3 DP - 2024 Mar TI - BCG infection dose guides dendritic cell migration and T cell priming in the draining lymph node. PG - e13342 LID - 10.1111/sji.13342 [doi] AB - 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-Guerin (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 (10(4) to 10(6) 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 24 hour after infection and was independent of BCG dose over a 10-fold range (10(5) to 10(6) 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. CI - (c) 2023 The Authors. Scandinavian Journal of Immunology published by John Wiley & Sons Ltd on behalf of The Scandinavian Foundation for Immunology. FAU - Krmeska, Veronika AU - Krmeska V AUID- ORCID: 0000-0001-8094-6266 AD - Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden. FAU - Shen, Lei AU - Shen L AD - Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden. FAU - Nylen, Susanne AU - Nylen S AD - Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden. FAU - Wowk, Pryscilla Fanini AU - Wowk PF AD - Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden. AD - Instituto Carlos Chagas, Fundacao Oswaldo Cruz (ICC/Fiocruz-PR), Curitiba, Brazil. FAU - Rothfuchs, Antonio Gigliotti AU - Rothfuchs AG AUID- ORCID: 0000-0001-6001-7240 AD - Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden. LA - eng GR - Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior/ GR - Instituto Carlos Chagas, Fundacao Oswaldo Cruz/ GR - Karolinska Institutet/ GR - Vetenskapsradet/ PT - Journal Article DEP - 20231121 PL - England TA - Scand J Immunol JT - Scandinavian journal of immunology JID - 0323767 RN - 0 (BCG Vaccine) SB - IM MH - Mice MH - Animals MH - Guinea Pigs MH - *T-Lymphocytes MH - *BCG Vaccine MH - Immunity, Cellular MH - Langerhans Cells MH - Lymph Nodes OTO - NOTNLM OT - BCG OT - dose OT - lymph node EDAT- 2024/03/05 12:44 MHDA- 2024/03/06 06:43 CRDT- 2024/03/05 10:03 PHST- 2023/10/11 00:00 [revised] PHST- 2023/05/26 00:00 [received] PHST- 2023/11/09 00:00 [accepted] PHST- 2024/03/06 06:43 [medline] PHST- 2024/03/05 12:44 [pubmed] PHST- 2024/03/05 10:03 [entrez] AID - 10.1111/sji.13342 [doi] PST - ppublish SO - Scand J Immunol. 2024 Mar;99(3):e13342. doi: 10.1111/sji.13342. Epub 2023 Nov 21.