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- Title
Modulation of Innate Antigen-Presenting Cell Function by Pre-patent Schistosome Infection.
- Authors
Ferragine, Christine E.; Walls, Colleen D.; Davies, Stephen J.
- Abstract
Schistosomes are intravascular helminths that infect over 200 million people worldwide. Deposition of eggs by adult schistosomes stimulates Th2 responses to egg antigens and induces granulomatous pathology that is a hallmark of schistosome infection. Paradoxically, schistosomes require host immune function for their development and reproduction and for egress of parasite eggs from the host. To identify potential mechanisms by which immune cells might influence parasite development prior to the onset of egg production, we assessed immune function in mice infected with developing schistosomes. We found that pre-patent schistosome infection is associated with a loss of T cell responsiveness to other antigens and is due to a diminution in the ability of innate antigen-presenting cells to stimulate T cells. Diminution of stimulatory capacity by schistosome worms specifically affected CD11b+ cells and did not require concomitant adaptive responses. We could not find evidence for production of a diffusible inhibitor of T cells by innate cells from infected mice. Rather, inhibition of T cell responsiveness by accessory cells required cell contact and only occurred when cells from infected mice outnumbered competent APCs by more than 3∶1. Finally, we show that loss of T cell stimulatory capacity may in part be due to suppression of IL-12 expression during pre-patent schistosome infection. Modulation of CD4+ T cell and APC function may be an aspect of host immune exploitation by schistosomes, as both cell types influence parasite development during pre-patent schistosome infection. Author Summary: The disease schistosomiasis is caused by a parasitic blood fluke found mainly in the tropics and subtropics and affects over 200 million people worldwide. Using mice to model human schistosome infection, our previous studies showed that schistosome development in the infected host is linked to host immune function, such that parasite development is impaired in hosts with immunological deficiencies. CD4+ T cells and cells of the monocyte/macrophage lineage are two types of immune cells that are involved in modulating schistosome development. In this study, we examined immune function in mice infected with developing schistosomes, to gain insights into how immune cells might influence parasite development. We found evidence of broad-spectrum suppression of CD4+ T cell responses during early schistosome infection. We also show that the loss of T cell responsiveness is due to impairment of T cell stimulation by CD11b+ cells. These findings suggest that exploitation of CD4+ T cells and monocytes/macrophages by schistosomes may involve parasite modification of the function of these cells.
- Subjects
CELL physiology; ANTIGEN presenting cells; T cells; IMMUNODEFICIENCY; SCHISTOSOMA; T cell receptors
- Publication
PLoS Neglected Tropical Diseases, 2013, Vol 7, Issue 3, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0002136