The retinoic acid-producing capacity of gut dendritic cells and macrophages is reduced during persistent T. muris infection.
Bottom Line: Vitamin A and its active metabolite retinoic acid are strongly linked with the modulation of gut immune responses.Further, during an on-going T. muris infection, ALDH expression is repressed from uninfected levels and only recovers to normal levels following expulsion of the parasite.These results suggest that local regulation of cellular levels of retinoic acid is an important component of infection-driven inflammation.
Affiliation: Faculty of Life Sciences, The University of Manchester, Manchester, UK. email@example.comShow MeSH
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Mentions: To establish whether the production of retinoic acid changes over the course of an acute and/or chronic T. muris infection, the ALDEFLUOR assay was used to measure the expression of aldehyde dehydrogenases (ALDH) in large intestinal macrophages and dendritic cells (DCs). ALDH enzymes are responsible for the production of retinoic acid from its precursors, and their expression is tightly regulated 13. Acute T. muris infection was modelled in C57BL/6 mice given a high-dose infection (expulsion complete by day 21 p.i.). Chronic infection was modelled in both AKR mice given a high-dose infection and C57BL/6 mice given a low-dose infection. Thus, lamina propria leucocytes were isolated from the colons of chronically infected AKR mice, chronically infected C57BL/6 mice and acutely infected C57BL/6 mice at 7-day intervals and FACS stained. The phenotyping of gut macrophages and DCs is complex and controversial 18, 19. In this study, macrophages were defined as 7AAD-CD45+MHCII+CD103-F4/80+CD11b+ cells and DCs were defined as 7AAD-CD45+MHCII+CD103+F4/80-CD11c+ cells (Fig. 1a). Percentages of macrophage and DC populations expressing ALDH were analysed rather than total numbers of cells, as is it impossible to determine total numbers of cells given the way cells were extracted from the gut.
Affiliation: Faculty of Life Sciences, The University of Manchester, Manchester, UK. firstname.lastname@example.org