Abstract
Schistosoma mansoni uses different mechanisms to escape its host’s immunity. Understanding the ability of memory T cells to withstand this pathogen’s manipulation is important for the development of effective vaccines against this immunomodulatory pathogen. In this study, ovalbumin (OVA) transgenic S. mansoni is used as a tool to investigate whether fully differentiated Th1, Th2 and Th17 cells are able to withstand pathogen manipulation. Naïve T cells from OT-II T cell receptor transgenic mice with a specificity for OVA were differentiated into Th1, Th2, and Th17 polarised memory cells in vitro. These cells were adoptively transferred into recipient mice to investigate whether these polarised immune memory T cells are resilient in the face of pathogen-mediated manipulation. After transferring memory cells, mice were challenged with OVA-transduced S. mansoni eggs as well as wild-type controls. The in vitro differentiated Th1, Th2 and Th17 memory cells continued to produce the same cytokines when challenged by OVA-expressing S. mansoni eggs as to these they produced when transferred in vivo, suggesting that the Th phenotypes of the memory T cells remains unaltered in the face of stimulation by S. mansoni. The ability of memory T cells to remain resilient to manipulation by the parasite suggests that vaccines might be able to produce immune memory responses able to withstand S. mansoni immune manipulation and hence protect the host from infection.
Highlights
Long-lasting protective immunity against a pathogen, in a host, is most often achieved through the development of pathogen-specific immune memory T cells that can be restimulated during the early phase of the infection
While the mechanisms of T cell manipulation by S. mansoni eggs are well understood for naïve T cells, it is unclear whether this manipulation takes place against fully differentiated immune memory T cells with an established T helper phenotype bias
This result appears in contradiction with the observation that S. mansoni eggs induce a Th2 response during in vivo infection
Summary
Long-lasting protective immunity against a pathogen, in a host, is most often achieved through the development of pathogen-specific immune memory T cells that can be restimulated during the early phase of the infection. S. mansoni secretory excretory antigens (SEA), produced in the egg-stage of the parasite, have the ability to manipulate human or mouse DCs to suppress classical maturation of co-stimulatory ligand expression These manipulated DCs induce a Th2 response in vitro following a transfer to a naïve host under MyD88- and IL-4-independent conditions [4]. While the mechanisms of T cell manipulation by S. mansoni eggs are well understood for naïve T cells, it is unclear whether this manipulation takes place against fully differentiated immune memory T cells with an established T helper phenotype bias This understanding of whether parasites are able to influence an established immune memory response during the recall phase is critical to vaccination strategies relying on immune memory T cells able to withstand pathogen manipulation
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