In vitro antigen presenting cell-derived IL-10 and IL-6 correlate with Trichuris muris isolate-specific survival.
Trichuris muris, the mouse whipworm, is used as a laboratory model of the human parasite T. trichiura. Three laboratory isolates of T. muris exist - the E, J and S isolates. Previous data have shown that the S isolate survives to chronicity in C57BL/6 mice unlike the E and J isolates, which are expelled. The ability of the S isolate to persist is thought to be due to it secreting unique excretory/secretory antigens, which interact with APCs such that protective T cell responses do not develop. To determine whether APCs respond differently to E/S antigens from the three isolates we cultured isolate-specific E/S with bone marrow-derived macrophages (BMMPhi) and dendritic cells (BMDCs) in vitro. Markers of co-stimulation and levels of MHC-II were analysed by FACS and cytokine levels in supernatants quantified. E/S antigens from the S isolate consistently stimulated significantly higher levels of IL-10 and IL-6 from both macrophages (F4/80(+)CD11b(+)CD11c(-)) and dendritic cells (CD11c(+)CD11b(+)F4/80(-)) compared to J and E isolate E/S. If these in vitro differences in APC-derived cytokines, particularly IL-10, are biologically significant in vivo, they may contribute to the S isolate survival, by creating a regulatory cytokine environment in which protective immune responses are less effective.
D'Elia
R
R
University of Manchester, UK. riccardo.d'elia@postgrad.manchester.ac.uk
Else
K J
KJ
D000818:Animals; D000938:Antigen-Presenting Cells / Q000737:chemistry / Q000276:immunology*; D015703:Antigens, CD / Q000032:analysis; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D016753:Interleukin-10 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008264:Macrophages / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D014257:Trichuriasis / Q000276:immunology*; D014258:Trichuris / Q000276:immunology*
D015703:Antigens, CD; D000949:Histocompatibility Antigens Class II; D015850:Interleukin-6; D016753:Interleukin-10