Association between skin reactivity to HDM or cockroach and potential risk factors for atopy in the semi-urban area^a.

a<p>association based on univariate logistic model. ^bMean and standard deviation.¹diagnosed by PCR. ²diagnosed by microscopy. The number of positives (n) of the total population examined (N). OR: Odds ratio, CI: Confidence intervals. *P<0.05.</p

Association between specific or total IgE and potential risk factors for atopy in the semi-urban area^a.

a<p>association based on univariate logistic model. ^bMean and standard deviation. The total population examined (N). ^#IgE to <i>Dermatophagoides pteronyssinus</i> (HDM). ¹diagnosed by PCR. ²diagnosed by microscopy. β (beta): estimate regression coefficients. CI: Confidence intervals. *P<0.05, **P<0.01, ***P<0.001.</p

Association between skin reactivity, specific IgE or total IgE and potential risk factors for atopy in the semi-urban area^a.

a<p>Multivariate model adjusted with age and sex. β (beta): estimate regression coefficients. CI: Confidence intervals. *P<0.05, **P<0.01, ***P<0.001, ^¶P<0.1.</p

Characteristics of population and allergic disorders in semi-urban and rural areas.

<p>SD: standard deviation. The number of positives (n) of the total population examined (N). ^#IgE to <i>Dermatophagoides pteronyssinus</i> (HDM).</p><p>The statistically significant results are given in bold. ^$P-value derived from Student t-test. ^∞P-value derived from Chi-Square test.</p

Immune parameters in soil-transmitted helminth uninfected and infected participants.

<p>Abbreviations: HsCRP = High sensitive C reactive protein, TNF = tumor necrosis factor, IL10 = interleukin 10, IgE = Immunoglobulin E. HsCRP, TNF, IL10 and IgE are log-transformed.</p><p># The difference is expressed as increase or decrease in the parameter per increasing number of infections per patient (maximum = 3).</p><p>Immune parameters in soil-transmitted helminth uninfected and infected participants.</p

The association of number of soil-transmitted helminth species per subject and Homeostasis Model Assessment for insulin Resistance (HOMAIR).

<p>The association of number of helminth species infections with HOMAIR (mean, 95%CI) with correction for age, sex, and BMI. The numbers of participants with none, one, two or at least three species were respectively 161, 189, 98 and 29. The p for linear trend is 0.01. *Adjusted mean for HOMAIR were derived from linear regression. White circle = no soil-transmitted helminth infection; black circle = infected with one soil-transmitted helminth species; white square = infected with two soil-transmitted helminth species; black square = infected with at least three soil-transmitted helminth species.</p

Dectin-1/2–induced autocrine PGE₂ signaling licenses dendritic cells to prime Th2 responses

<div><p>The molecular mechanisms through which dendritic cells (DCs) prime T helper 2 (Th2) responses, including those elicited by parasitic helminths, remain incompletely understood. Here, we report that soluble egg antigen (SEA) from <i>Schistosoma mansoni</i>, which is well known to drive potent Th2 responses, triggers DCs to produce prostaglandin E2 (PGE₂), which subsequently—in an autocrine manner—induces OX40 ligand (OX40L) expression to license these DCs to drive Th2 responses. Mechanistically, SEA was found to promote PGE₂ synthesis through Dectin-1 and Dectin-2, and via a downstream signaling cascade involving spleen tyrosine kinase (Syk), extracellular signal-regulated kinase (ERK), cytosolic phospholipase A₂ (cPLA₂), and cyclooxygenase 1 and 2 (COX-1 and COX-2). In addition, this pathway was activated independently of the actions of omega-1 (ω-1), a previously described Th2-priming glycoprotein present in SEA. These findings were supported by in vivo murine data showing that ω-1–independent Th2 priming by SEA was mediated by Dectin-2 and Syk signaling in DCs. Finally, we found that Dectin-2^−/−, and to a lesser extent Dectin-1^−/− mice, displayed impaired Th2 responses and reduced egg-driven granuloma formation following <i>S</i>. <i>mansoni</i> infection, highlighting the physiological importance of this pathway in Th2 polarization during a helminth infection. In summary, we identified a novel pathway in DCs involving Dectin-1/2-Syk-PGE₂-OX40L through which Th2 immune responses are induced.</p></div

Parameters of glucose metabolism parameters in soil-transmitted helminth uninfected and infected participants.

<p>Abbreviations: BMI = body mass index, WHR = waist to hip ratio, FBG = fasting blood glucose, HOMAIR = Homeostasis model assessment for insulin resistance.</p><p>* WHR is calculated by waist circumference (cm) / hip circumference (cm)</p><p>** HOMAIR index is calculated with HOMAIR formula = fasting serum insulin x fasting glucose / 22.5, using HOMA2 calculator (<a href="https://www.dtu.ox.ac.uk/homacalculator/" target="_blank">https://www.dtu.ox.ac.uk/homacalculator/</a>)</p><p># The difference is expressed as increase or decrease in the parameter per increasing number of helminth species per patient (maximum = 3). Insulin and HOMAIR were log-transformed.</p><p>Parameters of glucose metabolism parameters in soil-transmitted helminth uninfected and infected participants.</p

Characteristics of the study population.

<p>Abbreviations: BMI = body mass index, WHR = waist to hip ratio, FBG = fasting blood glucose, HOMAIR = Homeostasis model assessment for insulin resistance, HsCRP = High sensitive C reactive protein, TNF = tumor necrosis factor, IL10 = interleukin 10, IgE = Immunoglobulin E.</p><p>^*after logarithmic transformation</p><p>Characteristics of the study population.</p

Infection with Soil-Transmitted Helminths Is Associated with Increased Insulin Sensitivity

<div><p>Objective</p><p>Given that helminth infections have been shown to improve insulin sensitivity in animal studies, which may be explained by beneficial effects on energy balance or by a shift in the immune system to an anti-inflammatory profile, we investigated whether soil-transmitted helminth (STH)-infected subjects are more insulin sensitive than STH-uninfected subjects.</p><p>Design</p><p>We performed a cross-sectional study on Flores island, Indonesia, an area with high prevalence of STH infections.</p><p>Methods</p><p>From 646 adults, stool samples were screened for <i>Trichuris trichiura</i> by microscopy and for <i>Ascaris lumbricoides</i>, <i>Necator americanus</i>, <i>Ancylostoma duodenale</i>, <i>and Strongyloides stercoralis</i> by qPCR. No other helminth was found. We collected data on body mass index (BMI, kg/m²), waist-to-hip ratio (WHR), fasting blood glucose (FBG, mmol/L), insulin (pmol/L), high sensitive C-reactive protein (ng/ml) and Immunoglobulin E (IU/ml). The homeostatic model assessment for insulin resistance (HOMAIR) was calculated and regression models were used to assess the association between STH infection status and insulin resistance.</p><p>Results</p><p>424 (66%) participants had at least one STH infection. STH infected participants had lower BMI (23.2 vs 22.5 kg/m², p value = 0.03) and lower HOMAIR (0.97 vs 0.81, p value = 0.05). In an age-, sex- and BMI-adjusted model a significant association was seen between the number of infections and HOMAIR: for every additional infection with STH species, the HOMAIR decreased by 0.10 (p for linear trend 0.01). This effect was mainly accounted for by a decrease in insulin of 4.9 pmol/L for every infection (p for trend = 0.07).</p><p>Conclusion</p><p>STH infections are associated with a modest improvement of insulin sensitivity, which is not accounted for by STH effects on BMI alone.</p></div