Details

Autor(en) / Beteiligte

• Prendergast, Catriona T
• Sanin, David E
• Mountford, Adrian P

Titel

Alternatively activated mononuclear phagocytes from the skin site of infection and the impact of IL-4R[alpha] signalling on CD4.sup.+T cell survival in draining lymph nodes after repeated exposure to Schistosoma mansoni cercariae

Ist Teil von

• PLoS neglected tropical diseases, 2016-08, Vol.10 (8)

Ort / Verlag

Public Library of Science

Erscheinungsjahr

2016

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• In a murine model of repeated exposure of the skin to infective Schistosoma mansoni cercariae, events leading to the priming of CD4 cells in the skin draining lymph nodes were examined. The dermal exudate cell (DEC) population recovered from repeatedly (4x) exposed skin contained an influx of mononuclear phagocytes comprising three distinct populations according to their differential expression of F4/80 and MHC-II. As determined by gene expression analysis, all three DEC populations (F4/80.sup.- MHC-II.sup.high, F4/80.sup.+ MHC-II.sup.high, F4/80.sup.+ MHC-II.sup.int) exhibited major up-regulation of genes associated with alternative activation. The gene encoding RELM[alpha] (hallmark of alternatively activated cells) was highly up-regulated in all three DEC populations. However, in 4x infected mice deficient in RELM[alpha], there was no change in the extent of inflammation at the skin infection site compared to 4x infected wild-type cohorts, nor was there a difference in the abundance of different mononuclear phagocyte DEC populations. The absence of RELM[alpha] resulted in greater numbers of CD4.sup.+ cells in the skin draining lymph nodes (sdLN) of 4x infected mice, although they remained hypo-responsive. Using mice deficient for IL-4R[alpha], in which alternative activation is compromised, we show that after repeated schistosome infection, levels of regulatory IL-10 in the skin were reduced, accompanied by increased numbers of MHC-II.sup.high cells and CD4.sup.+ T cells in the skin. There were also increased numbers of CD4.sup.+ T cells in the sdLN in the absence of IL-4R[alpha] compared to cells from singly infected mice. Although their ability to proliferate was still compromised, increased cellularity of sdLN from 4x IL-4R[alpha]KO mice correlated with reduced expression of Fas/FasL, resulting in decreased apoptosis and cell death but increased numbers of viable CD4.sup.+ T cells. This study highlights a mechanism through which IL-4R[alpha] may regulate the immune system through the induction of IL-10 and regulation of Fas/FasL mediated cell death.