Rapid induction of IgE responses to a worm cysteine protease during murine pre-patent schistosome infection.

Background: During the pre-patent stage of infection, juvenile Schistosoma blood flukes co-opt signals from the adaptive immune system to facilitate parasite development, but the types of responses that are induced at this early stage of infection, and the parasite antigens they target, have not been characterized.

Results: Through analysis of experimental pre-patent infections, we show that the S. mansoni cysteine protease SmCB1 is rapidly targeted by an antigen-specific IgE response.

Blood fluke exploitation of non-cognate CD4+ T cell help to facilitate parasite development.

Schistosoma blood flukes, which infect over 200 million people globally, co-opt CD4+ T cell-dependent mechanisms to facilitate parasite development and egg excretion. The latter requires Th2 responses, while the mechanism underpinning the former has remained obscure. Using mice that are either defective in T cell receptor (TCR) signaling or that lack TCRs that can respond to schistosomes, we show that naïve CD4+ T cells facilitate schistosome development in the absence of T cell receptor signaling.

Structural and functional characterization of SporoSAG: a SAG2-related surface antigen from Toxoplasma gondii.

Toxoplasma gondii, the etiological agent of toxoplasmosis, utilizes stage-specific expression of antigenically distinct glycosylphosphatidylinositol-tethered surface coat proteins to promote and establish chronic infection. Of the three infective stages of T. gondii, sporozoites are encapsulated in highly infectious oocysts that have been linked to large scale outbreaks of toxoplasmosis.

Decrease of Foxp3+ Treg cell number and acquisition of effector cell phenotype during lethal infection.

Using a model of lethal oral infection with Toxoplasma gondii, we examined the fate of both induced and natural regulatory T (Treg) cells in the face of strong inflammatory responses occurring in a tolerogenic-prone environment. We found that during highly T helper 1 (Th1) cell-polarized mucosal immune responses, Treg cell numbers collapsed via multiple pathways, including blockade of Treg cell induction and disruption of endogenous Treg cell homeostasis. In particular, shutdown of interleukin 2 (IL-2) in the highly Th1 cell-polarized environment triggered by infection directly contributes to Treg cell incapacity to suppress effector responses and eventually leads to immunopathogenesis.

Conservation of CD4+ T cell-dependent developmental mechanisms in the blood fluke pathogens of humans.

Schistosoma blood flukes are trematode parasites with a cosmopolitan distribution that infect over 200 million people globally. We previously showed that Schistosoma mansoni growth and development in the mammalian host is dependent on signals from host CD4+ T cells. To gain insight into the mechanisms that underlie this dependence, we sought to determine the evolutionary origins and limits of this aspect of the host-pathogen relationship.

The common gamma chain cytokines interleukin (IL)-2 and IL-7 indirectly modulate blood fluke development via effects on CD4+ T cells.

The human pathogen Schistosoma mansoni exhibits a highly evolved and intricate relationship with its host, evading immune destruction while co-opting CD4(+) T cell-driven mechanisms to facilitate parasite development and egg excretion. Because the common gamma ( gamma (c)) chain cytokine interleukin (IL)-7 is also implicated in modulating schistosome development, we investigated whether this effect is mediated indirectly through the essential role that IL-7 plays in CD4(+) T cell growth and survival. We demonstrate that attenuated schistosome development in the absence of IL-7 results from dysregulated T cell homeostasis and not from disruption of direct interactions between schistosomes and IL-7.

Receptor use by pathogenic arenaviruses.

The arenavirus family contains several important human pathogens including Lassa fever virus (LASV), lymphocytic choriomeningitis virus (LCMV) and the New World clade B viruses Junin (JUNV) and Machupo (MACV). Previously, alpha-dystroglycan (alpha-DG) was identified as a receptor recognized by LASV and certain strains of LCMV. However, other studies have suggested that alpha-DG is probably not used by the clade B viruses, and the receptor(s) for these pathogens is currently unknown.

The Tetratricopeptide repeat domain 7 gene is mutated in flaky skin mice: a model for psoriasis, autoimmunity, and anemia.

The flaky skin (fsn) mutation in mice causes pleiotropic abnormalities including psoriasiform dermatitis, anemia, hyper-IgE, and anti-dsDNA autoantibodies resembling those detected in systemic lupus erythematosus. The fsn mutation was mapped to an interval of 3.9 kb on chromosome 17 between D17Mit130 and D17Mit162.

Requirements for the development of IL-4-producing T cells during intestinal nematode infections: what it takes to make a Th2 cell in vivo.

Components of the type 2 immune response may mediate host protection against both helminthic parasites and harmful allergic responses. A central player in this response is the T-helper 2 (Th2) effector cell, which produces interleukin (IL)-4, IL-5, IL-13, and other Th2 cytokines during the primary and memory response. Specific aspects of the parasite that trigger Th2-cell differentiation are not yet defined.