Activation of the NLRP3 inflammasome by Mycobacterium tuberculosis is uncoupled from susceptibility to active tuberculosis.

As a hallmark of tuberculosis (TB), Mycobacterium tuberculosis (MTB) induces granulomatous lung lesions and systemic inflammatory responses during active disease. Molecular regulation of inflammation is associated with inflammasome assembly. We determined the extent to which MTB triggers inflammasome activation and how this impacts on the severity of TB in a mouse model. MTB stimulated release of mature IL-1β in macrophages while attenuated M. bovis BCG failed to do so. Tubercle bacilli specifically activated the NLRP3 inflammasome and this propensity was strictly controlled by the virulence-associated RD1 locus of MTB. However, Nlrp3-deficient mice controlled pulmonary TB, a feature correlated with NLRP3-independent production of IL-1β in infected lungs. Our studies demonstrate that MTB activates the NLRP3 inflammasome in macrophages in an ESX-1-dependent manner. However, during TB, MTB promotes NLRP3- and caspase-1-independent IL-1β release in myeloid cells recruited to lung parenchyma and thus overcomes NLRP3 deficiency in vivo in experimental models.

Association between mannose-binding lectin (MBL) deficiency and cytomegalovirus (CMV) infection after kidney transplantation

MBLdeficiency is thought to be a risk factor for the development of viral infection, such as genital herpes and HSV-2 meningitis. However, there is limited data on the possible interaction between MBL and CMV, especially after organ transplantation. Between 2003 and 2005, we measured MBL levels in 16 kidney transplant recipients with high-risk CMV serostatus (donor positive/recipient negative, D+/R−). All patients receivedCMV prophylaxis of valganciclovir 450 mg/day for 3 months after transplantation. After stopping valganciclovir, CMV-DNA was measured in whole blood by real time PCR every 2 weeks for 3 months. CMV infections were diagnosed according to the recommendations of the AST. MBL levels were measured in stored pre-transplantation sera by an investigator blinded to the CMV complications. MBL levels below 500 ng/ml were considered as being functionally deficient. After a follow-up of at least 10 months, seven patients out of 16 developed CMV disease (three CMV syndrome, and four probable invasive disease, i.e. two colitis and two hepatitis), four patients developed asymptomatic CMV infection, and five patients never developed any sign of CMV replication. Peak CMV-DNA was higher in patients with CMV disease than in those with asymptomatic infection (4.64 versus 2.72 mean log copy CMV-DNA/106 leukocytes, p < 0.05). Overall, 9/16 patients (56%) had MBL deficiency: 5/7 (71%) of patients with CMV disease, 4/4 (100%) of patients with asymptomatic CMVinfection, and 0/5 (0%) of patients withoutCMVinfection (p < 0.005, between CMV infection/disease versus no infection or control blood donors). There were no significant differences in age, gender or immunosuppressive regimens between the groups. MBL deficiency may be a significant risk factor for the development of post-prophylaxisCMVinfection in D+/R−kidney recipients, suggesting a new role of innate immunity in the control of CMV infection after organ transplantation.

Low adiponectin is associated with increased ambulatory pulse pressure and activation of the renin-angiotensin system in subjects of African descent

Purpose: Adiponectin, arterial stiffness, as well components of the renin-angiotensin system are associated with cardiovascular risk. This study was aimed to investigate whether plasma adiponectin was directly linked with pulse pressure (PP), as a marker for arterial stiffness, and the renin-angiotensin system (RAS). Methods and materials: A family-based study in subjects of African descent enriched with hypertensive patients was carried out in the Seychelles. Fasting plasma adiponectin was determined by ELISA, plasma renin activity according to the antibody-trapping principle and plasma aldosterone by radioimmunoassay. Daytime ambulatory blood pressure (BP) was measured using Diasys Integra devices. PP was calculated as the difference between systolic and diastolic BP. The association of adiponectin with PP, plasma renin activity and plasma aldosterone were analyzed using generalized estimating equations with a gaussian family link and an exchangeable correlation structure to account for familial aggregation. Results: Data from 335 subjects from 73 families (152 men, 183 women) were available. Men and women had mean (SD) age of 45.4 ± 11.1 and 47.3 ± 12.4 years, BMI of 26.3 ± 4.4 and 27.8 ± 5.1 kg/m2, daytime systolic/diastolic BP of 132.6 ± 15.4 / 86.1 ± 10.9 and 130 ± 17.6 / 83.4 ± 11.1 mmHg, and daytime PP of 46.5 ± 9.9 and 46.7 ± 10.7 mmHg, respectively. Plasma adiponectin was 4.4± 3.04 ng/ml in men and 7.39 ± 5.44 ng/ml in women (P <0.001). After adjustment for age, sex and BMI, log-transformed adiponectin was negatively associated with daytime PP (-0.009 ± 0.003, P = 0.004), plasma renin activity (-0.248 ± 0.080, P = 0.002) and plasma aldosterone (-0.004 ± 0.002, P = 0.014). Conclusion: Low adiponectin is associated with increased ambulatory PP and RAS activation in subjects of African descent. Our data are consistent with the observation that angiotensin II receptor blockers increase adiponectin in humans.

Integration or individuation : are the salvation goods promised by first-century Christian preaching still attractive ?

(Résumé de l'ouvrage) The idea that religion has to succeed in a «market», selling «salvation goods», has proved to be extremely attractive to scholars in sociology and the study of religion. Max Weber used the term «salvation good» to compare different religious traditions. Pierre Bourdieu employed the term in order to analyze «religious economy». And recently, an American group of researchers advocating «rational choice of religion» put the theme at the forefront of current debates. This book - the fruit of an International Congress in Lausanne in April 2005 - brings together leading specialists in the fields of sociology and the study of religion who discuss the terms «salvation goods» (or religious goods) and «religious market». The authors test the applicability of these concepts by using specific examples and they either deliberately advocate or criticize Weberian, Bourdieusian or rational-choice perspectives.

SITC 26th annual meeting - summary.

ABSTRACT: The 26th annual meeting of the Society for Immunotherapy of Cancer took place in Bethesda on November 4 to 6, 2011 and was organized by Charles G. Drake (Johns Hopkins University) Dolores J. Schendel (Helmholtz Zentrum Muenchen - German Research Center for Environmental Health Institute of Molecular Immunology), Jeffrey Schlom (National Cancer Institute, National Institutes of Health), and Jedd D. Wolchok (Memorial Sloan-Kettering Cancer Center). It was an event marked by a number of extraordinary circumstances: it attracted a record attendance of 805 participants from 24 different countries. The gathering came in the wake of great as well as very sad news for the tumor immunology community. Good news included the approval of anti-CTLA-4 as a therapy for metastatic melanoma in April and the announcement in early October of the Nobel Prize in Physiology and Medicine awarded to pioneering studies in the field of immunology. Indeed, one part of the prize went to Dr. Bruce Beutler, Scripps Research Institute, La Jolla, USA and Dr. Jules Hoffman, Institute for Molecular Cell Biology, Strasbourg, France, for their discoveries in innate immunity and the other part to Dr. Ralph Steinman, The Rockfeller University, New York, for his discovery of dendritic cells. Sad news was the losses of two giants in the field. Jürg Tschopp of the University of Lausanne in March and Ralph Steinman, who passed away just three days before his Nobel Prize announcement. The loss of these two charismatic scientific leaders was particularly sad for the Annual Meeting as both J. Tschopp and R. Steinman were confirmed speakers at this meeting: the former to deliver the keynote lecture and the latter as recipient of the Richard V. Smalley prize.

6.2

Airborne particles can come from a variety of sources and contain variable chemical constituents. Some particles are formed by natural processes, such as volcanoes, erosion, sea spray, and forest fires, while other are formed by anthropogenic processes, such as industrial- and motor vehicle-related combustion, road-related wear, and mining. In general, larger particles (those greater than 2.5 μm) are formed by mechanical processes, while those less than 2.5 μm are formed by combustion processes. The chemical composition of particles is highly influenced by the source: for combustion-related particles, factors such as temperature of combustion, fuel type, and presence of oxygen or other gases can also have a large impact on PM composition. These differences can often be observed at a regional level, such as the greater sulphate-composition of PM in regions that burn coal for electricity production (which contains sulphur) versus regions that do not. Most countries maintain air monitoring networks, and studies based on the resulting data are the most common basis for epidemiology studies on the health effects of PM. Data from these monitoring stations can be used to evaluate the relationship between community-level exposure to ambient particles and health outcomes (i.e., morbidity or mortality from various causes). Respiratory and cardiovascular outcomes are the most commonly assessed, although studies have also considered other related specific outcomes such as diabetes and congenital heart disease. The data on particle characteristics is usually not very detailed and most often includes some combination of PM2.5, PM10, sulphate, and NO2. Other descriptors that are less commonly found include particle number (ultrafine particles), metal components of PM, local traffic intensity, and EC/OC. Measures of association are usually reported per 10 μg/m3 or interquartile range increase in pollutant concentration. As the exposure data are taken from regional monitoring stations, the measurements are not representative of an individual's exposure. Particle size is an important descriptor for understanding where in the human respiratory system the particles will deposit: as a general rule, smaller particles penetrate to deeper regions of the lungs. Initial studies on the health effects of particulate matter focused on mass of the particles, including either all particles (often termed total suspended particulate or TSP) or PM10 (all particles with an aerodynamic diameter less than 10 μm). More recently, studies have considered both PM10 and PM2.5, with the latter corresponding more directly to combustion-related processes. UFPs are a dominant source of particles in terms of PNC, yet are negligible in terms of mass. Very few epidemiology studies have measured the effect of UFPs on health; however, the numbers of studies on this topic are increasing. In addition to size, chemical composition is of importance when understanding the toxicity of particles. Some studies consider the composition of particles in addition to mass; however this is not common, in part due the cost and labour involved in such analyses.