Functional specialization of memory Th cells revealed by expression of integrin CD49b

Infection or immunization induces heterogeneous memory T cell subsets, but their origin and protective value against infection are unclear. In this study, we report the functional characterization of two memory Th subsets, defined by expression of integrin CD49b. Stable CD49b expression is induced in up to one-half of all memory Th cells. More importantly, the CD49b- and CD49b+ subsets display distinct helper activities, typified by the production of IL-10 and TNF-alpha, respectively. Although the inflammatory properties of the CD49b+ subset are protective against intracellular bacterial infection, they are associated with immunopathology in acute viral infection. Modulation of the CD49b-defined memory Th subsets may provide infection type-specific interventions, where either enhancement of the inflammatory response or reduction of immunopathology is essential.     

Regulation and function of innate and adaptive interleukin-17-producing cells

Interleukin-17 (IL-17)-mediated immune responses play a crucial role in the mucosal host defence against microbial and fungal pathogens. However, the chronic activation of IL-17-producing T helper cells can cause autoimmune disease. In addition, recent studies have highlighted key roles of innate cell-mediated IL-17 responses in various inflammatory settings. Besides inflammation, there have also been intriguing findings regarding the involvement of IL-17 responses in the pathogenesis of cardiovascular diseases and tumour formation. Here, we discuss the latest discoveries in regulation and function of innate and adaptive IL-17-producing cells.     

Natural selection drives parallel divergence in the mountain plant Heliosperma pusillum s.l

The evolution of species or ecotypes can occur gradually through neutral and adaptive genetic changes. To explore the influence of natural selection during early phases of divergence, morphological and ecological discontinuity and its adaptive significance were investigated in six pairs of alpine and independently evolved montane populations of Heliosperma pusillum s.l.; the latter are usually taxonomically recognised at the species rank in spite of their highly debatable taxonomic value. We tested whether environmental conditions – characterised by Landolt indicator values from vegetation surveys and temperature measurements – and morphology of alpine and montane populations differ discretely and in parallel across six population pairs. By reciprocal transplantation experiments in natural environments in two population pairs and in climate chambers for five population pairs we compared fitness of native versus non‐native individuals. Alpine and montane populations differed in environmental conditions and morphology within each pair. Morphological differentiation occurred in parallel and correlated with environmental, but not with genetic distances. In both environments, native individuals had higher establishment success and plant size. Differentiation of the independently evolved montane populations is driven by natural selection and parallel, independent adaptation in response to drought, lower irradiance and higher, less fluctuating temperatures in montane populations. Our study system exemplifies rapid, parallel evolution leading to morphologically and ecologically strongly divergent, though fully interfertile, ecotypes.     

Induction of Red Color Formation in Cabbage Juice by Lactobacillus brevis and Its Relationship to Pink Sauerkraut

Membrane-filtered cabbage juice, when fermented by Lactobacillus brevis under conditions of controlled pH, frequently produced a water-soluble red pigment. The pigment, presumably responsible for imparting a highly objectionable discoloration to sauerkraut, was formed during the post logarithmic phase of growth. Color development is pH dependent (5.2 to 6.3) and can be suppressed by chemical reductants or anaerobic conditions of growth. The compound responsible for discoloration was purified and partially characterized.     

Molecular cross-talk in host-parasite relationships: the intriguing immunomodulatory role of Echinococcus antigen B in cystic echinococcosis

Cystic echinococcosis (CE), a zoonosis caused by the development of Echinococcus granulosus tapeworm larvae in the internal organs of ungulates and humans, continues to pose a major public health burden in underdeveloped and industrialised areas worldwide. Research designed to improve parasitic disease control and find out more about parasite biology has already identified a number of E. granulosus antigenic molecules. The major E. granulosus immunomodulant antigen isolated from hydatid fluid is antigen B, a 120kDa polymeric lipoprotein consisting of various 8kDa subunits. By inhibiting elastase activity and neutrophil chemotaxis and eliciting a non-protective Th2 cell response, antigen B helps the parasite evade the human response. In this review, we briefly discuss current information on the molecular characteristics and immunomodulatory properties of E. granulosus antigen B. Besides focusing on findings that provide intriguing insights into the complex interplay between host and parasite, we suggest how this information could extend the current therapeutic options in inflammatory diseases.     

Measuring respiratory symptoms of COPD: performance of the EXACT- Respiratory Symptoms Tool (E-RS) in three clinical trials

Background

Symptomatic relief is an important treatment goal for patients with COPD. To date, no diary for evaluating respiratory symptoms in clinical trials has been developed and scientifically-validated according to FDA and EMA guidelines. The EXACT – Respiratory Symptoms (E-RS) scale is a patient-reported outcome (PRO) measure designed to address this need. The E-RS utilizes 11 respiratory symptom items from the existing and validated 14-item EXACT, which measures symptoms of exacerbation. The E-RS total score quantifies respiratory symptom severity, and 3 domains assess breathlessness, cough and sputum, and chest symptoms.

Methods

This study examined the performance of the E-RS in each of 3 controlled trials with common and unique validation variables: one 6-month (N = 235, US) and two 3-month (N = 749; N = 597; international). Subjects completed the E-RS as part of a daily eDiary. Tests of reliability, validity, and responsiveness were conducted in each dataset.

Results

In each study, RS-Total score was internally consistent (Cronbach α) (0.88, 0.92, 0.92) and reproducible (intra-class correlation) in stable patients (2 days apart: 0.91; 7 days apart: 0.71, 0.74). RS-Total scores correlated significantly with the following criterion variables (Spearman’s rho; p < 0.01, all comparisons listed here): FEV₁% predicted (−0.19, −0.14, −0.15); St. George’s Respiratory Questionnaire (SGRQ) (0.65, 0.52, 0.51); Breathlessness, Cough, and Sputum Scale (BCSS) (0.89, 0.89); modified Medical Research Council dyspnoea scale (mMRC) (0.40); rescue medication use (0.43, 0.42); Functional Performance Inventory Short-Form (FPI-SF) (0.43); 6-minute walk distance (6-MWT) (−0.30, −0.14) and incremental shuttle walk (ISWT) (−0.18) tests. Correlations between these variables and RS-Breathlessness, RS-Cough and Sputum, RS-Chest Symptoms scores supported subscale validity. RS-Total, RS-Breathlessness, and RS-Chest Symptoms differentiated mMRC levels of breathlessness severity (p < 0.0001). RS-Total and domain scores differentiated subjects with no rescue medication use and 3 or more puffs (p < 0.0001). Sensitivity to changes in health status (SGRQ), symptoms (BCSS), and exercise capacity (6MWT, ISWT) were also shown and responder definitions using criterion- and distribution-based methods are proposed.

Conclusions

Results suggest the E-RS is a reliable, valid, and responsive measure of respiratory symptoms of COPD suitable for use in natural history studies and clinical trials.

Trial registration

MPEX: {"type":"clinical-trial","attrs":{"text":"NCT00739648","term_id":"NCT00739648"}}NCT00739648; AZ1: {"type":"clinical-trial","attrs":{"text":"NCT00949975","term_id":"NCT00949975"}}NCT00949975; AZ 2: {"type":"clinical-trial","attrs":{"text":"NCT01023516","term_id":"NCT01023516"}}NCT01023516

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-014-0124-z) contains supplementary material, which is available to authorized users.