T-zone localized monocyte-derived dendritic cells promote Th1 priming to Salmonella

Adriana Flores-Langarica, Jennifer L. Marshall, Saeeda Bobat, Elodie Mohr, Jessica Hitchcock, Ewan A. Ross, Ruth E. Coughlan, Mahmood Khan, Nico Van Rooijen, Ian R. Henderson, Ian C.M. MacLennan, Adam F. Cunningham*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Control of intracellular Salmonella infection requires Th1 priming and IFN-γ production. Here, we show that efficient Th1 priming after Salmonella infection requires CD11c +CD11b hiF4/80 + 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-γ production via a TNF-α-dependent mechanism. Importantly, moDCs and cDCs when co-cultured induced superior Th1 differentiation than either subset alone, and this activity was independent of TNF-α. Thus, optimal Th1 development to Salmonella requires the rapid accumulation of moDCs within T zones and their collaboration with cDCs.

Original languageEnglish
Pages (from-to)2654-2665
Number of pages12
JournalEuropean Journal of Immunology
Volume41
Issue number9
DOIs
Publication statusPublished - 1 Sep 2011

Keywords

  • APCs
  • DCs
  • Infectious diseases
  • Salmonella
  • T helper cell

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