Age-Related Patterns in Human Myeloid Dendritic Cell Populations in People Exposed to Schistosoma haematobium Infection

Abstract

Background

Urogenital schistosomiasis is caused by the helminth parasite Schistosoma haematobium. In high transmission areas, children acquire schistosome infection early in life with infection levels peaking in early childhood and subsequently declining in late childhood. This age-related infection profile is thought to result from the gradual development of protective acquired immunity. Age-related differences in schistosome-specific humoral and cellular responses have been reported from several field studies. However there has not yet been a systematic study of the age-related changes in human dendritic cells, the drivers of T cell polarisation.

Methods

Peripheral blood mononuclear cells were obtained from a cohort of 61 Zimbabwean aged 5–45 years with a S. haematobium prevalence of 47.5%. Two subsets of dendritic cells, myeloid and plasmacytoid dentritic cells (mDCs and pDCs), were analyzed by flow cytometry.

Findings

In this population, schistosome infection levels peaked in the youngest age group (5–9 years), and declined in late childhood and adulthood (10+ years). The proportions of both mDCs and pDCs varied with age. However, for mDCs the age profile depended on host infection status. In the youngest age group infected people had enhanced proportions of mDCs as well as lower levels of HLA-DR on mDCs than un-infected people. In the older age groups (10–13 and 14–45 years) infected people had lower proportions of mDCs compared to un-infected individuals, but no infection status-related differences were observed in their levels of HLA-DR. Moreover mDC proportions correlated with levels of schistosome-specific IgG, which can be associated with protective immunity. In contrast proportions of pDCs varied with host age, but not with infection status.

Conclusions

Our results show that dendritic cell proportions and activation in a human population living in schistosome-endemic areas vary with host age reflecting differences in cumulative history of exposure to schistosome infection.

Author Summary

A characteristic feature of most helminth infections is the convex age infection profile, where infection levels rise to peak in early childhood and decline in adulthood, a pattern thought to result from the development of protective acquired immunity. Thus, several investigations characterizing protective responses to inform vaccine research have focused on responses present in older people, who despite continued exposure to infection carry little or no infection. To date, such studies have identified key responses which are correlates of resistance. However, there is a paucity of information on cell types that are mediators rather than effectors of the immune responses. One such group where there are limited studies in human schistosome infections is dendritic cells which are important for the polarizations of CD4+ T cell responses. Therefore, we characterized the age profile of dendritic cells in Zimbabweans exposed to Schistosoma haematobium infection. We found an age-related pattern in the proportions of myeloid dendritic cells (a subset of dendritic cells) in this population. Furthermore, in the case myeloid dendritic cells, the age profile differed between schistosome infected and un-infected people. Thus our study suggests that activation and migration of myeloid dendritic cells also develop in an age-related pattern consistent with the cumulative history of exposure to schistosome parasites.