Variation in host susceptibility and infectiousness generated by co-infection: the myxoma–Trichostrongylus retortaeformis case in wild rabbits

One of the conditions that can affect host susceptibility and parasite transmission is the occurrence of concomitant infections. Parasites interact directly or indirectly within an individual host and often these interactions are modulated by the host immune response. We used a free-living rabbit population co-infected with the nematode Trichostrongylus retortaeformis, which appears to stimulate an acquired immune response, and the immunosuppressive poxvirus myxoma. Modelling was used to examine how myxoma infection alters the immune-mediated establishment and death/expulsion of T. retortaeformis, and consequently affects parasite intensity and duration of the infection. Simulations were based on the general TH1–TH2 immunological paradigm that proposes the polarization of the host immune response towards one of the two subsets of T helper cells. Our findings suggest that myxoma infections contribute to alter host susceptibility to the nematode, as co-infected rabbits showed higher worm intensity compared with virus negative hosts. Results also suggest that myxoma disrupts the ability of the host to clear T. retortaeformis as worm intensities were consistently high and remained high in old rabbits. However, the co-infection model has to include some immune-mediated nematode regulation to be consistent with field data, indicating that the TH1–TH2 dichotomy is not complete. We conclude that seasonal myxoma outbreaks enhance host susceptibility to the nematode and generate highly infected hosts that remain infectious for a longer time. Finally, the virus–nematode co-infection increases heterogeneities among individuals and potentially has a large effect on parasite transmission

From teratocarcinomas to embryonic stem cells.

The recent derivation of human embryonic stem (ES) cell lines, together with results suggesting an unexpected degree of plasticity in later, seemingly more restricted, stem cells (so-called adult stem cells), have combined to focus attention on new opportunities for regenerative medicine, as well as for understanding basic aspects of embryonic development and diseases such as cancer. Many of the ideas that are now discussed have a long history and much has been underpinned by the earlier studies of teratocarcinomas, and their embryonal carcinoma (EC) stem cells, which present a malignant surrogate for the normal stem cells of the early embryo. Nevertheless, although the potential of EC and ES cells to differentiate into a wide range of tissues is now well attested, little is understood of the key regulatory mechanisms that control their differentiation. Apart from the intrinsic biological interest in elucidating these mechanisms, a clear understanding of the molecular process involved will be essential if the clinical potential of these cells is to be realized. The recent observations of stem-cell plasticity suggest that perhaps our current concepts about the operation of cell regulatory pathways are inadequate, and that new approaches for analysing complex regulatory networks will be essential