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Group 2 innate lymphoid cells (ILC2s) play crucial roles in type 2 immune responses associated with allergic and autoimmune diseases, viral and helminth infections and tissue homeostasis. Experimental models show that in helminth infections ILC2s provide an early source of type 2 cytokines and therefore are essential for the induction of potentially protective type 2 responses. Much of our knowledge of ILC2s in helminth infections has come from experimental mouse models with very few studies analysing ILC2s in natural human infections. In attempts to harness knowledge from paradigms of the development of protective immunity in human helminth infections for vaccine development, the role of ILC2 cells could be pivotal. So far, potential vaccines against human helminth infections have failed to provide effective protection when evaluated in human studies. In addition to appropriate antigen selection, it is apparent that more detailed knowledge on mechanisms of induction and maintenance of protective immune responses is required. Therefore, there is need to understand how ILC2 cells induce type 2 responses and subsequently support the development of a protective immune response in the context of immunizations. Within this review, we summarize the current knowledge of the biology of ILC2s, discuss the importance of ILC2s in human helminth infections and explore how ILC2 responses could be boosted to efficiently induce protective immunity. This article is protected by copyright. All rights reserved.

Evening trap and hlc collections (4â 7Â pm) for dry season and wet season. (DOCX 106Â kb)

Demographic sistribution of volunteers in study communities. (DOCX 83Â kb)

Overnight trap collections for dry season and wet season (6Â pm â 6Â am). (DOCX 67Â kb)

SUMMARY To combat schistosomiasis, the World Health Organization (WHO) recommends that infection levels are determined prior to designing and implementing control programmes, as the treatment regimens depend on the population infection prevalence. However, the sensitivity of the parasitological infection diagnostic method is less reliable when infection levels are low. The aim of this study was to compare levels of Schistosoma haematobium infection obtained by the parasitological method vs serological technique. Infection levels in preschool and primary school-aged children and their implications for control programmes were also investigated. Infection prevalence based on serology was significantly higher compared with that based on parasitology for both age groups. The difference between infection levels obtained using the two methods increased with age. Consequentially, in line with the WHO guidelines, the serological method suggested a more frequent treatment regimen for this population compared with that implied by the parasitological method. These findings highlighted the presence of infection in children aged ⩽5 years, further reiterating the need for their inclusion in control programmes. Furthermore, this study demonstrated the importance of using sensitive diagnostic methods as this has implications on the required intervention controls for the population.

Schistosomiasis is a major public health problem in Africa. However, it is only recently that the burden of schistosomiasis has become recognised as a significant component impacting on the health, wellbeing and development of infants and preschool children (aged ≤5 years). A longitudinal study was conducted in Zimbabwean children to determine the effect of single praziquantel treatment on Schistosoma haematobium-related morbidity markers: microhaematuria, proteinuria, and albuminuria. Changes in these indicators were compared in 1–5 years versus 6–10 years old to determine if treatment outcomes differed by age-group. Praziquantel was efficacious at reducing infection 12 weeks post-treatment: cure rate=94.6%; (95% CI: 87.9–97.7%). Infection rates remained lower 12 months post-treatment compared to baseline in both age-groups. Among children who received praziquantel, the odds of presenting with two markers of morbidity 12 weeks post-treatment were significantly lower compared to baseline; proteinuria: odds ratio, OR=0.54; (95% CI: 0.31–0.95), and albuminuria: OR=0.05; (95% CI: 0.02–0.14). Levels of microhaematuria significantly reduced 12 months post-treatment, and the effect of praziquantel did not differ between the two age-groups: OR=0.97; (95% CI: 0.50–1.87). Praziquantel treatment has health benefits in preschool-aged children exposed to S. haematobium and the efficacy of praziquantel on infection and morbidity is not age-dependent.

The CD3ζ forms part of the T cell receptor (TCR) where it plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways leading to T cell effector functions. Down regulation of CD3ζ leads to impairment of immune responses including reduced cell proliferation and cytokine production. In experimental models, helminth parasites have been shown to modulate immune responses directed against them and unrelated antigens, so called bystander antigens, but there is a lack of studies validating these observations in humans. This study investigated the relationship between expression levels of the TCR CD3ζ chain with lymphocyte cell proliferation during human infection with the helminth parasite, Schistosoma haematobium, which causes uro-genital schistosomiasis. Using flow cytometry, peripheral blood mononuclear cells (PBMCs) from individuals naturally exposed to S. haematobium in rural Zimbabwe were phenotyped, and expression levels of CD3ζ on T cells were related to intensity of infection. In this population, parasite infection intensity was inversely related to CD3ζ expression levels (p < 0.05), consistent with downregulation of CD3ζ expression during helminth infection. Furthermore, PBMC proliferation was positively related to expression levels of CD3ζ (p < 0.05) after allowing for confounding variables (host age, sex, and infection level). CD3ζ expression levels had a differing relationship between immune correlates of susceptibility and immunity, measured by antibody responses, indicating a complex relationship between immune activation status and immunity. The relationships between the CD3ζ chain of the TCR and schistosome infection, PBMC proliferation and schistosome-specific antibody responses have not previously been reported, and these results may indicate a mechanism for the impaired T cell proliferative responses observed during human schistosome infection.

Background MicroRNAs (miRNAs) are a class of short non-coding RNA that play important roles in disease processes in animals and are present in a highly stable cell-free form in body fluids. Here, we examine the capacity of host and parasite miRNAs to serve as tissue or serum biomarkers of Schistosoma mansoni infection. Methods/Principal Findings We used Exiqon miRNA microarrays to profile miRNA expression in the livers of mice infected with S. mansoni at 7 weeks post-infection. Thirty-three mouse miRNAs were differentially expressed in infected compared to naïve mice (>2 fold change, p, Author Summary Schistosomiasis is a chronic disease caused by blood flukes that affects over 200 million people worldwide, of which 90% live in Sub-Saharan Africa. In the field setting schistosomiasis caused by S. mansoni is diagnosed by detection of parasite eggs in stool samples using microscopic techniques. Here we investigate the potential of microRNAs (miRNAs), a class of short noncoding RNAs, to act as biomarkers of S. mansoni infection. We have identified a specific subset of murine miRNAs whose expression is significantly altered in the liver between 6–12 weeks post infection. However their abundance in serum is not significantly different between naïve and S. mansoni-infected mice until twelve weeks post infection and they do not display consistent differential abundance in the serum of infected versus uninfected humans. In contrast, three parasite-derived miRNAs (miR-277, bantam and miR-3479-3p) were detected in the serum of infected mice and human patients and the combined detection of these miRNAs could distinguish S. mansoni infected from uninfected individuals from low and high infection intensity areas with 89%/80% or 80%/90% specificity/sensitivity, respectively. These results demonstrate that miRNAs of parasite origin are a new class of serum biomarker for detecting S. mansoni and likely other helminth infections.

Human IgG1 antibody responses are associated with protection against Schistosoma haematobium infection and are now a target for schistosome vaccine development. This study aimed to investigate the relationship between total IgG and the IgG subclasses and the monocyte IgG receptor, known as FcγRIIIa or CD16, in schistosome exposed people. Systemic levels of schistosome-specific anti-adult worm total IgG and IgG subclass titres were measured by ELISA in 100 individuals from an S. haematobium endemic area in Zimbabwe and, using parametric statistical methods and regression analysis, related to the levels of CD16 expression on individuals' circulating monocytes, determined via flow cytometry. Monocyte CD16 expression rose with parasite-specific total IgG and IgG1 in healthy participants, but not in schistosome infected patients. Similar to parasite-specific IgG and IgG1, CD16 expression in healthy individuals is associated with protection against schistosome infection. This relationship indicates a mechanistic link between the innate and adaptive immune responses to helminth infection in protection against infection. Further understanding the elements of a protective immune response in schistosomiasis may aid in efforts to develop a protective vaccine against this disease., Author Summary Schistosomiasis is a parasitic disease caused by the parasite Schistosoma spp. Over 240 million people are infected worldwide, mainly in Sub-Saharan Africa, but an efficacious, protective vaccine has yet to be found. Protection against schistosome infection in individuals living in endemic areas is mediated by antibodies. In particular, IgG1 antibody has been shown to be protective against infection in individuals living in endemic areas, and eliciting IgG1 production has become a cornerstone of vaccine development efforts. However, little is known about the mechanisms by which IgG1 induces protection. The cell surface molecule CD16 is an IgG antibody receptor expressed on monocytes and binds preferentially to IgG antibody subclasses. The work presented here thus investigates the relationship between IgG levels and the monocyte CD16 receptor in a population endemically exposed to infection with schistosomes. We present results linking CD16 expression with IgG1 levels, whereby uninfected individuals have a positive relationship between IgG1 and CD16 expression levels, while schistosome infected individuals did not show any statistically significant relationship between the two. Thus we provide evidence to suggest a mechanistic link between the innate and adaptive immune response in parasitic infection, associating monocyte CD16 expression with a protective immune response.