Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 41, Issue 9, Pages 2654-2665Publisher
WILEY-BLACKWELL
DOI: 10.1002/eji.201141440
Keywords
APCs; DCs; Infectious diseases; Salmonella; T helper cell
Categories
Funding
- BBSRC
- BBSRC [BB/F022778/1] Funding Source: UKRI
- MRC [G0900857, G8402371, G0701275] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/F022778/1] Funding Source: researchfish
- Medical Research Council [G8402371, G9818340B, G0701275, G9818340, G0900857] Funding Source: researchfish
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Control of intracellular Salmonella infection requires Th1 priming and IFN-gamma production. Here, we show that efficient Th1 priming after Salmonella infection requires CD11c(+) CD11b(hi)F4/80(+) monocyte-derived dendritic cells (moDCs). In non-infected spleens, moDCs are absent from T-cell zones (T zones) of secondary lymphoid tissues, but by 24h post-infection moDCs are readily discernible in these sites. The accumulation of moDCs is more dependent upon bacterial viability than bacterial virulence. Kinetic studies showed that moDCs were necessary to prime but not sustain Th1 responses, while ex vivo studies showed that antigen-experienced moDCs were sufficient to induce T-cell proliferation and IFN-gamma production via a TNF-alpha-dependent mechanism. Importantly, moDCs and cDCs when co-cultured induced superior Th1 differentiation than either subset alone, and this activity was independent of TNF-alpha. Thus, optimal Th1 development to Salmonella requires the rapid accumulation of moDCs within T zones and their collaboration with cDCs.
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