TLRs, Treg, and B Cells, an Interplay of Regulation during Helminth Infection

Commonly described as masters of regulation parasitic helminth infections provide a fascinating insight into the complexity of our immune system. As with many other pathogens helminths have developed complex evasion strategies and the immune response of the host has to find a balance between eliciting severe damage to eliminate the parasite or limiting damage and thereby accepting the infection. Nevertheless, one should not forget that these infections still pose a serious public health problem and can elicit severe disfigurement or death in the individual. An interesting spin-off of helminth manipulation on host responses is the apparent prevention of autoimmune diseases or allergy although the actual mechanisms remain unclear. It is well known that Toll-like-receptors (TLR) and non-TLR PRRs play a critical role in initiating innate immune responses which in turn create appropriate adaptive immune reactions. Helminths comprise of a multitude of (glyco)-proteins and (glyco)-lipids and some have been shown to trigger TLR, or alter TLR-mediated responses. Such reactions of course alter adaptive immunity as well. This review will address the consequences of TLR-triggering by helminth antigens and the downstream effect on B cell and regulatory T cell (Treg) actions

Reductions in microfilaridermia by repeated ivermectin treatment are associated with lower Plasmodium-specific Th17 immune responses in Onchocerca volvulus-infected individuals

Background: 37 million individuals are currently infected with Onchocerca volvulus (O. volvulus), a parasitic nematode that elicits various dermal manifestations and eye damage in man. Disease control is primarily based on distributing ivermectin in mass drug administration (MDA) programmes which aim at breaking transmission by eliminating microfilariae (MF), the worm's offspring. The majority of infected individuals present generalized onchocerciasis, which is characterized by hyporesponsive immune responses and high parasite burden including MF. Recently, in areas that have been part of MDA programmes, individuals have been identified that present nodules but are amicrofilaridermic (a-MF) and our previous study showed that this group has a distinct immune profile. Expanding on those findings we determined the immune responses of O. volvulus-infected individuals to a Plasmodium-derived antigen MSP-1 (merozoite surface protein-1), which is required by the parasite to enter erythrocytes. Methods: Isolated PBMCs from O. volvulus-infected individuals (164 MF+ and 46 a-MF) and non-infected volunteers from the same region (NEN), were stimulated with MSP-1 and the resulting supernatant screened for the presence of IL-5, IL-13, IFN-γ, TNF-α, IL-6, IL-17A and IL-10. These findings were then further analyzed following regression analysis using the covariates MF, ivermectin (IVM) and region. The latter referred to the Central or Ashanti regions of Ghana, which, at the time sampling, had received 8 or 1 round of MDA respectively. Results: IL-5, IL-13 and IFN-γ responses to MSP-1 were not altered between NEN and O. volvulus-infected individuals nor were any associations revealed in the regression analysis. IL-10, IL-6 and TNF-α MSP-1 responses were, however, significantly elevated in cultures from infected individuals. Interestingly, when compared to a-MF individuals, MSP-induced IL-17A responses were significantly higher in MF+ patients. Following multivariable regression analysis these IL-10, IL-6, TNF-α and IL-17A responses were all dominantly associated with the regional covariate. Conclusions: Consequently, areas with a lowered infection pressure due to IVM MDA appear to influence bystander responses to Plasmodium-derived antigens in community members even if they have not regularly participated in the therapy

A randomized trial of deferred stenting versus immediate stenting to prevent no- or slow-reflow in acute ST-segment elevation myocardial infarction (DEFER-STEMI)

Objectives: The aim of this study was to assess whether deferred stenting might reduce no-reflow and salvage myocardium in primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Background: No-reflow is associated with adverse outcomes in STEMI. Methods: This was a prospective, single-center, randomized, controlled, proof-of-concept trial in reperfused STEMI patients with ≥1 risk factors for no-reflow. Randomization was to deferred stenting with an intention-to-stent 4 to 16 h later or conventional treatment with immediate stenting. The primary outcome was the incidence of no-/slow-reflow (Thrombolysis In Myocardial Infarction ≤2). Cardiac magnetic resonance imaging was performed 2 days and 6 months after myocardial infarction. Myocardial salvage was the final infarct size indexed to the initial area at risk. Results: Of 411 STEMI patients (March 11, 2012 to November 21, 2012), 101 patients (mean age, 60 years; 69% male) were randomized (52 to the deferred stenting group, 49 to the immediate stenting). The median (interquartile range [IQR]) time to the second procedure in the deferred stenting group was 9 h (IQR: 6 to 12 h). Fewer patients in the deferred stenting group had no-/slow-reflow (14 [29%] vs. 3 [6%]; p = 0.006), no reflow (7 [14%] vs. 1 [2%]; p = 0.052) and intraprocedural thrombotic events (16 [33%] vs. 5 [10%]; p = 0.010). Thrombolysis In Myocardial Infarction coronary flow grades at the end of PCI were higher in the deferred stenting group (p = 0.018). Recurrent STEMI occurred in 2 patients in the deferred stenting group before the second procedure. Myocardial salvage index at 6 months was greater in the deferred stenting group (68 [IQR: 54% to 82%] vs. 56 [IQR: 31% to 72%]; p = 0.031]. Conclusions: In high-risk STEMI patients, deferred stenting in primary PCI reduced no-reflow and increased myocardial salvage

Distinct Immune Profiles of Exhausted Effector and Memory CD8+ T Cells in Individuals With Filarial Lymphedema

CD8+ T cells are crucial for the clearance of viral infections, and current research begins to highlight their importance in parasitic diseases too. In-depth research about characteristics of CD8+ T-cell subsets and exhaustion remains uncertain, especially during filariasis, a chronic helminth infection. Lymphatic filariasis, elicited by Wuchereria bancrofti, remains a serious health problem in endemic areas in Ghana, especially in those suffering from morbidity due to lymphedema (LE). In this observational study, the characteristics and profiles of CD8+ T cells were compared between asymptomatic Wuchereria bancrofti-infected individuals, uninfected endemic normals, and those with LE (grades 2–6). Focusing on exhausted memory (CD8+exmem: CD8+ T-betdimEomeshi) and effector (CD8+exeff: CD8+T-bethiEomesdim) CD8+ T-cell subsets, advanced flow cytometry revealed that LE individuals presented reduced frequencies of IFN-γ+CD8+exmem T cells expressing Tim-3 or LAG-3 which negatively correlated to the presence of LE. Moreover, the LE cohort further showed significantly higher frequencies of IL-10+CD8+exeff T cells expressing either Tim-3, LAG-3, CD39, KLRG-1, or PD-1, all associated markers of exhaustion, and that these frequencies positively correlated with the presence of LE. In summary, this study shows that distinct exhausted CD8+ T-cell subsets are prominent in individuals suffering from LE, suggesting that enhanced inflammation and constant immune activation might drive exhaustion of CD8+ T cells. Since T-cell exhaustion is known to be associated with insufficient control of persisting antigen, the data presented here reveals that these CD8+ T-cell exhaustion patterns in filarial LE should be taken into consideration for prevention and control management of LE

Emotional burnout of specialists in socio-occupational professions: contemporary views on the problem

Представлено сучасні підходи до проблеми вигорання у представників соціономічних професій у контексті емоційної праці, емоційного і когнітивного дисонансу. Проаналізовано й узагальнено наукову літературу з питань вигорання, визначено три основні його компоненти: емоційне і/або фізичне виснаження, зниження продуктивності праці і надмірна деперсоналізація. На основі аналізу визначень вигорання встановлено його зв’язок з емоційною працею (регуляцією і вираженням емоційних станів). Обстоюється думка, що фахівці соціономічних професій особливо вразливі до вигорання, оскільки тривалий час перебувають у стані, коли необхідно постійно контролювати свої емоції, брати на себе відповідальність і відчувати невизначеність, працюючи з іншими людьми. Емоційну працю розглянуто як предиктор вигорання у фахівців соціономічних професій. На основі аналізу літератури, присвяченої проблемам вигорання та емоційного дисонансу, висловлено припущення, що вимоги щодо емоційної праці зумовлюють різноманітність проявів синдрому виго-рання (у тому числі виснаження, цинізму, зниження продуктивності праці та погіршення самопочуття), а знання симптомів вигорання дало б змогу фахівцям соціономічних професій запобігти виникненню та загостренню цього стану.This article deals with the modern approaches to the problem of burnout of helping professionals in the context of emotional labor, emotional and cognitive dissonance. The burnout literature is reviewed, compared, and summarized. The definition of burnout is proposed including three components: emotional and/or physical exhaustion, lowered work productivity, and excessive depersonalization. Based on an analysis of the definitions of burnout, the paper focuses on the connec-tion of burnout and emotional work (regulation of feelings and emotional expression). It is also maintained a fact that helping professionals are especially vulnerable to burnout because of the necessity to control own emotions for a long time, to take responsibilities, and to feel uncertainties they encounter while working with others. The current study discussed emotional labor as a predictor of burnout of helping professionals. On the basis of the literature on burnout and emotional dissonance, the author of this article hypothesized that emotional job demands would explain variances of burnout (i.e., exhaustion and cynicism). Knowledge of abovementioned syndromes would help socionomy professionals to avoid emergence and aggravation of emotional burnout.Представлены современные подходы к проблеме выгорания у представителей социономических профессий в контексте эмоциональной труда, эмоционального и когнитивного диссонанса. Проанализированы и обобщены научную литературу по вопросам выгорания, определены три основные его компоненты: эмоциональное и / или физическое истощение, снижение производительности труда и чрезмерная деперсонализация. На основе анализа определений выгорания установлена ​​его связь с эмоциональной трудом (регуляцией и выражением эмоциональных состояний). Отстаивается мнение, что специалисты социономических профессий особенно уязвимы к выгоранию, поскольку длительное время находятся в состоянии, когда необходимо постоянно контролировать свои эмоции, брать на себя ответственность и чувствовать неопределенность, работая с другими людьми. Эмоциональный труд рассмотрен как предиктор выгорания у специалистов социономических профессий. На основе анализа литературы, посвященной проблемам выгорания и эмоционального диссонанса, высказано предположение, что требования по эмоциональной труда обусловливают разнообразие проявлений синдрома выгорания (в том числе истощения, цинизма, снижение производительности труда и ухудшение самочувствия), а знание симптомов выгорания позволило бы специалистам социономических профессий предотвратить возникновение и обострение этого состояния

Impact of helminth infections on female reproductive health and associated diseases

A growing body of knowledge exists on the influence of helminth infections on allergies and unrelated infections in the lung and gastrointestinal (GI) mucosa. However, the bystander effects of helminth infections on the female genital mucosa and reproductive health is understudied but important considering the high prevalence of helminth exposure and sexually transmitted infections in low- and middle-income countries (LMICs). In this review, we explore current knowledge about the direct and systemic effects of helminth infections on unrelated diseases. We summarize host disease-controlling immunity of important sexually transmitted infections and introduce the limited knowledge of how helminths infections directly cause pathology to female reproductive tract (FRT), alter susceptibility to sexually transmitted infections and reproduction. We also review work by others on type 2 immunity in the FRT and hypothesize how these insights may guide future work to help understand how helminths alter FRT health

Comparison of immune responses to Loa loa stage-specific antigen extracts in Loa loa-exposed BALB/c mice upon clearance of infection

Background: Different immune mechanisms are capable of killing developmental stages of filarial nematodes and these mechanisms are also likely to vary between the primary and a challenge infection. However, the lack of a detailed analysis of cytokine, chemokine and immunoglobulin levels in human loiasis is still evident. Therefore, detailed analysis of immune responses induced by the different developmental stages of Loa loa in immune-competent BALB/c mice will aid in the characterization of distinct immune responses that are important for the immunity against loiasis. Methods: Different developmental stages of L. loa were obtained from human peripheral blood (microfilariae, MF), the transmitting vector, Chrysops (larval stage 3, L3) and infected immune-deficient BALB/cRAG2γc−/− mice (L4, L5, adult worms). Groups of wildtype BALB/c mice were then injected with the isolated stages and after 42 days postinfection (pi), systemic cytokine, chemokine and immunoglobulin levels were determined. These were then compared to L. loa-specific responses from in vitro re-stimulated splenocytes from individual mice. All parameters were determined using Luminex technology. Results: In a pilot study, BALB/c mice cleared the different life stages of L. loa within 42 days pi and systemic cytokine, chemokine and munoglobulin levels were equal between infected and naive mice. Nevertheless, L. loa-specific re-stimulation of splenocytes from mice infected with L5, MF or adult worms led to induction of Th2, Th17 and chemokine secretion patterns. Conclusions: This study shows that although host immunity remains comparable to naive mice, clearance of L. loa life-cycle development stages can induce immune cell memory leading to cytokine, chemokine and mmunoglobulins secretion patterns which might contribute to immunity and protection against reinfection

Update on the distribution of Mansonella perstans in the southern part of Cameroon: influence of ecological factors and mass drug administration with ivermectin

Overview of gender distribution and median age in study sites. Out of 14,293 (6,746 males and 7,547 females) individuals involved in the study, 52.8 % were females. (PDF 224 kb

Toll-Like Receptors 2 and 4 Regulate the Frequency of IFNγ-Producing CD4+ T-Cells during Pulmonary Infection with Chlamydia pneumoniae

TLR2 and TLR4 are crucial for recognition of Chlamydia pneumoniae in vivo, since infected TLR2/4 double-deficient mice are unable to control the infection as evidenced by severe loss of body weight and progressive lethal pneumonia. Unexpectedly, these mice display higher pulmonary levels of the protective cytokine IFNγ than wild type mice. We show here, that antigen-specific CD4+ T-cells are responsible for the observed IFNγ-secretion in vivo and their frequency is higher in TLR2/4 double-deficient than in wild type mice. The capacity of TLR2/4 double-deficient dendritic cells to re-stimulate CD4+ T-cells did not differ from wild type dendritic cells. However, the frequency of CD4+CD25+Foxp3+ T-cells was considerably higher in wild type compared to TLR2/4 double-deficient mice and was inversely related to the number of IFNγ-secreting CD4+ effector T-cells. Despite increased IFNγ-levels, at least one IFNγ-mediated response, protective NO-secretion, could not be induced in the absence of TLR2 and 4. In summary, CD4+CD25+Foxp3+ regulatory T-cells fail to expand in the absence of TLR2 and TLR4 during pulmonary infection with C. pneumoniae, which in turn enhances the frequency of CD4+IFNγ+ effector T-cells. Failure of IFNγ to induce NO in TLR2/4 double-deficient cells represents one possible mechanism why TLR2/4 double-deficient mice are unable to control pneumonia caused by C. pneumoniae and succumb to the infection