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Langerin(+) CD8α(+) Dendritic Cells Drive Early CD8(+) T Cell Activation and IL-12 Production During Systemic Bacterial Infection

Bloodstream infections induce considerable morbidity, high mortality, and represent a significant burden of cost in health care; however, our understanding of the immune response to bacteremia is incomplete. Langerin(+) CD8α(+) dendritic cells (DCs), residing in the marginal zone of the murine splee...

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Detalles Bibliográficos
Autores principales: Prendergast, Kelly A., Daniels, Naomi J., Petersen, Troels R., Hermans, Ian F., Kirman, Joanna R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949331/
https://www.ncbi.nlm.nih.gov/pubmed/29867941
http://dx.doi.org/10.3389/fimmu.2018.00953
Descripción
Sumario:Bloodstream infections induce considerable morbidity, high mortality, and represent a significant burden of cost in health care; however, our understanding of the immune response to bacteremia is incomplete. Langerin(+) CD8α(+) dendritic cells (DCs), residing in the marginal zone of the murine spleen, have the capacity to cross-prime CD8(+) T cells and produce IL-12, both of which are important components of antimicrobial immunity. Accordingly, we hypothesized that this DC subset may be a key promoter of adaptive immune responses to blood-borne bacterial infections. Utilizing mice that express the diphtheria toxin receptor under control of the langerin promoter, we investigated the impact of depleting langerin(+) CD8α(+) DCs in a murine model of intravenous infection with Mycobacterium bovis bacille Calmette–Guerin (BCG). In the absence of langerin(+) CD8α(+) DCs, the immune response to blood-borne BCG infection was diminished: bacterial numbers in the spleen increased, serum IL-12p40 decreased, and delayed CD8(+) T cell activation, proliferation, and IFN-γ production was evident. Our data revealed that langerin(+) CD8α(+) DCs play a pivotal role in initiating CD8(+) T cell responses and IL-12 production in response to bacteremia and may influence the early control of systemic bacterial infections.