Small RNAs and extracellular vesicles in filarial nematodes: from nematode development to diagnostics

Parasitic nematodes have evolved sophisticated mechanisms to communicate with their hosts in order to survive and successfully establish an infection. The transfer of RNA within extracellular vesicles (EVs) has recently been described as a mechanism that could contribute to this communication in filarial nematodes. It has been shown that these EVs are loaded with several types of RNAs, including microRNAs, leading to the hypothesis that parasites could actively use these molecules to manipulate host gene expression and to the exciting prospect that these pathways could result in new diagnostic and therapeutic strategies. Here we review the literature on the diverse RNAi pathways that operate in nematodes and more specifically our current knowledge of extracellular RNA (exRNA) and EVs derived from filarial nematodes in vitro and within their hosts. We further detail some of the issues and questions related to the capacity of RNA-mediated communication to function in parasite-host interactions and the ability of exRNA to enable us to distinguish and detect different nematode parasites in their hosts

Сравнение электрохирургического и радиоволнового способов эксцизии полипов желудка

The work is based on the analysis of treatment of 162 patients with gastric polyps. A comparative analysis of electrosurgical and radio-wave methods of polypectomy was performed. The both methods of excision of gastric polyps were equally effective, and radio-wave polypectomy was accompanied by less number of complications. The results of long-term follow up propose a lower rate of recurrent polyps after radio-wave polypectomy.Статья посвящена актуальной проблеме эндоскопического лечения полипов желудка. В исследование включено 162 пациента с полипами желудка. Проведен сравнительный анализ электрохирургического и радиоволнового способов удаления полипов желудка. Оба способа эксцизии полипов желудка продемонстрировали сходную эффективность при меньшем уровне послеоперационных кровотечений после радиоволновой полипэктомии. Кроме того, применение радиоволнового способа эксцизии полипов желудка позволяет, по данным отдаленного обследования пациентов, уменьшить вероятность развития рецидивов полипов желудка

Wild immunology

In wild populations, individuals are regularly exposed to a wide range of pathogens. In this context, organisms must elicit and regulate effective immune responses to protect their health while avoiding immunopathology. However, most of our knowledge about the function and dynamics of immune responses comes from laboratory studies performed on inbred mice in highly controlled environments with limited exposure to infection. Natural populations, on the other hand, exhibit wide genetic and environmental diversity. We argue that now is the time for immunology to be taken into the wild. The goal of ‘wild immunology’ is to link immune phenotype with host fitness in natural environments. To achieve this requires relevant measures of immune responsiveness that are both applicable to the host–parasite interaction under study and robustly associated with measures of host and parasite fitness. Bringing immunology to nonmodel organisms and linking that knowledge host fitness, and ultimately population dynamics, will face difficult challenges, both technical (lack of reagents and annotated genomes) and statistical (variation among individuals and populations). However, the affordability of new genomic technologies will help immunologists, ecologists and evolutionary biologists work together to translate and test our current knowledge of immune mechanisms in natural systems. From this approach, ecologists will gain new insight into mechanisms relevant to host health and fitness, while immunologists will be given a measure of the real-world health impacts of the immune factors they study. Thus, wild immunology can be the missing link between laboratory-based immunology and human, wildlife and domesticated animal health

CTLA-4 and CD4+ CD25+ regulatory T cells inhibit protective immunity to filarial parasites in vivo

The T cell coinhibitory receptor CTLA-4 has been implicated in the down-regulation of T cell function that is a quintessential feature of chronic human filarial infections. In a laboratory model of filariasis, Litomosoides sigmodontis infection of susceptible BALB/c mice, we have previously shown that susceptibility is linked both to a CD4+ CD25+ regulatory T (Treg) cell response, and to the development of hyporesponsive CD4+ T cells at the infection site, the pleural cavity. We now provide evidence that L. sigmodontis infection drives the proliferation and activation of CD4+ Foxp3+ Treg cells in vivo, demonstrated by increased uptake of BrdU and increased expression of CTLA-4, Foxp3, GITR, and CD25 compared with naive controls. The greatest increases in CTLA-4 expression were, however, seen in the CD4+ Foxp3- effector T cell population which contained 78% of all CD4+ CTLA-4+ cells in the pleural cavity. Depletion of CD25+ cells from the pleural CD4+ T cell population did not increase their Ag-specific proliferative response in vitro, suggesting that their hyporesponsive phenotype is not directly mediated by CD4+ CD25+ Treg cells. Once infection had established, killing of adult parasites could be enhanced by neutralization of CTLA-4 in vivo, but only if performed in combination with the depletion of CD25+ Treg cells. This work suggests that during filarial infection CTLA-4 coinhibition and CD4+ CD25+ Treg cells form complementary components of immune regulation that inhibit protective immunity in vivo

Vaccination against filarial nematodes with irradiated larvae provides long-term protection against the third larval stage but not against subsequent life cycle stages

Sustainable control of human filariasis would benefit enormously from the development of an effective vaccine. The ability to vaccinate experimental animals, with reductions in worm burden of over 70%, suggests this aim is possible. However, in experimental vaccinations the challenge is usually administered 2 weeks after the immunisation phase and thus the protection obtained is likely to be biased by persisting inflammation. Using the murine model Litomosoides sigmodontis, we increased the time between immunisation with irradiated larvae and challenge with fully infective L3 to 5 months. Significant protection was achieved (54–58%) and the reduced worm burden was observed by 10 days p.i. The developmental stage targeted was the L3, since no nematodes died once they reached the pleural cavity of vaccinated mice, as has been previously shown in short-term protocols. However, larval developmental rate was faster in vaccinated than in primary-infected mice. Immunological assessments were made prior to challenge and then from 6 h to 34 days post-challenge. Samples were taken from the subcutaneous tissue where the larvae were inoculated, the lymph nodes through which they migrate and the pleural cavity in which they establish. Eosinophils were still present although scarce in the subcutaneous tissue of vaccinated mice before challenge. Cytokine and specific antibody production of vaccinated and challenged mice were L3-specific and Th2-biased and greatly exceeded the response of primary-infected mice. The heightened Th2 response may explain the faster development of the filarial worms in vaccinated mice. Thus, long-term vaccination protocols generated a strong memory response that led to significant but incomplete protection that was limited to the infective larval stage suggesting alternative vaccination strategies are needed

Wild immunology: converging on the real world

Recently, the Centre for Immunity, Infection and Evolution sponsored a one-day symposium entitled “Wild Immunology.” The CIIE is a new Wellcome Trust–funded initiative with the remit to connect evolutionary biology and ecology with research in immunology and infectious diseases in order to gain an interdisciplinary perspective on challenges to global health. The central question of the symposium was, “Why should we try to understand infection and immunity in wild systems?” Specifically, how does the immune response operate in the wild and how do multiple coinfections and commensalism affect immune responses and host health in these wild systems? The symposium brought together a broad program of speakers, ranging from laboratory immunologists to infectious disease ecologists, working on wild birds, unmanaged animals, wild and laboratory rodents, and on questions ranging from the dynamics of coinfection to how commensal bacteria affect the development of the immune system. The meeting on wild immunology, organized by Amy Pedersen, Simon Babayan, and Rick Maizels, was held at the University of Edinburgh on 30 June 2011