The activation status of human macrophages presenting antigen determines the efficiency of Th17 responses

Christina E. Arnold, Peter Gordon, Robert N. Barker, Heather M Wilson

Research output: Contribution to journalArticle

35 Citations (Scopus)
5 Downloads (Pure)

Abstract

Macrophages are antigen presenting cells that can adopt different activation states as directed by microenvironmental stimuli. It is well-recognised how CD4+ T helper (Th) signals drive macrophage activation, but the ability of differentially activated human macrophages to stimulate the major types of CD4+ T helper (Th) response by presenting antigen have not been well defined. Previous studies have focussed on murine cells, undifferentiated human monocytes, or macrophage products, and have been limited to non-physiological mitogenic Th responses. The aim was therefore to compare the Th cell polarising abilities of different human macrophage subsets when presenting specific antigen. We demonstrate for the first time that the way macrophages are activated, while naturally presenting antigen, has profound effects on downstream adaptive immune responses. In autologous co-cultures, LPS-activation was the most potent stimulus for antigen-loaded macrophages to drive Th17 polarisation from both unfractionated CD4+ T-cells and the CD45RO+ memory population, while IFNγ/LPS activated macrophages preferentially induced a Th1 phenotype. By contrast, IL-4-activated macrophages were ineffective in inducing responses by either Th subset. Although antigen-loaded dendritic cells were superior to macrophages in driving Th1 responses, the Th17 polarising capacity of the two antigen-presenting cell types was equivalent, and was strongly dependent on IL-1β secretion. Taken together, these results clearly demonstrate for the first time how differentially activated human macrophages present antigen to bias specific, rather than mitogen-driven, Th responses and lead us to propose that they impact adaptive immunity in vivo, particularly in determining Th17 polarisation within inflamed tissues
Original languageEnglish
Pages (from-to)10-19
Number of pages10
JournalImmunobiology
Volume220
Issue number1
Early online date13 Oct 2014
DOIs
Publication statusPublished - Jan 2015

Keywords

  • antigen presentation
  • human
  • macrophage activation
  • T cell polarisation
  • Th17

Fingerprint Dive into the research topics of 'The activation status of human macrophages presenting antigen determines the efficiency of Th17 responses'. Together they form a unique fingerprint.

  • Cite this