Human natural killer cells mediate adaptive immunity to viral antigens

Adaptive immune responses are defined as antigen sensitization–dependent and antigen-specific responses leading to establishment of long-lived immunological memory. Although natural killer (NK) cells have traditionally been considered cells of the innate immune system, mounting evidence in mice and nonhuman primates warrants reconsideration of the existing paradigm that B and T cells are the sole mediators of adaptive immunity. However, it is currently unknown whether human NK cells can exhibit adaptive immune responses. We therefore tested whether human NK cells mediate adaptive immunity to virally encoded antigens using humanized mice and human volunteers. We found that human NK cells displayed vaccination-dependent, antigen-specific recall responses in vitro, when isolated from livers of humanized mice previously vaccinated with HIV-encoded envelope protein. Furthermore, we discovered that large numbers of cytotoxic NK cells with a tissue-resident phenotype were recruited to sites of varicella-zoster virus (VZV) skin test antigen challenge in VZV-experienced human volunteers. These NK-mediated recall responses in humans occurred decades after initial VZV exposure, demonstrating that NK memory in humans is long-lived. Our data demonstrate that human NK cells exhibit adaptive immune responses upon vaccination or infection. The existence of human memory NK cells may allow for the development of vaccination-based approaches capable of establishing potent NK-mediated memory functions contributing to host protection

Las aventuras del Bachiller Trapaza

Copia digital. Valladolid : Junta de Castilla y León. Consejería de Cultura y Turismo, 2009-2010Escudo tip. en port

Basel II and fostering the disclosure of banks\' internal credit ratings

ISSN:1566-7529ISSN:1741-620

Early changes in inflammatory and pro-thrombotic biomarkers in patients initiating antiretroviral therapy with abacavir or tenofovir

<p>Abstract</p> <p>Background</p> <p>Abacavir has been associated with an increased risk of acute myocardial infarction, but the pathogenic mechanisms remain unknown. We evaluated longitudinal changes in pro-atherosclerotic biomarkers in patients initiating abacavir or tenofovir.</p> <p>Methods</p> <p>Consecutive patients initiating antiretroviral therapy (ART) with abacavir/lamivudine or tenofovir/emtricitabine were included. Plasma levels of high sensitivity C reactive protein (hsCRP), interleukin-6 (IL-6), intercellular adhesion molecule-1, vascular cell adhesion molecule-1 (sVCAM-1) and plasminogen activator inhibitor-1 (PAI-1) were measured at baseline and at different time points throughout 48 weeks. Comparisons were adjusted for age, sex, ART status at inclusion, viral load, lipodystrophy, Framingham score and hepatitis C virus co-infection status.</p> <p>Results</p> <p>50 patients were analyzed, 28 initiating abacavir and 22 tenofovir. The endothelial biomarker sVCAM-1 declined significantly in both treatment groups. hsCRP tended to increase soon after starting therapy with abacavir, a trend that was not seen in those initiating tenofovir. IL-6 significantly increased only at week 24 from baseline in patients on abacavir (+225%, p < 0.01) although the differences were not significant between groups. The procoagulant biomarker PAI-1 plasma levels increased from baseline at week 12 (+57%; p = 0.017), week 24 (+72%; p = 0.008), and week 48 (+149%; p < 0.001) in patients on tenofovir, but differences between groups were not statistically significant.</p> <p>Conclusion</p> <p>Changes in biomarkers of inflammation, coagulation, and endothelial function are not different in viremic patients starting ART with abacavir/lamivudine or tenofovir/emtricitabine. These changes occur in the early phases of treatment and include anti- and pro-atherosclerotic effects with both drugs.</p

The Role of Spirituality Healing with Perceptions of the Medical Encounter among Latinos

Little is known about the relationship between spirituality healing and perceptions about the medical encounter among Latinos. To examine the association between spirituality healing and attitudes of self-reported perceptions about the medical encounter. A cross-sectional telephone survey. 3,728 Latinos aged ≥18 years residing in the United States from Wave 1 of the Pew Hispanic Center/Robert Wood Johnson Foundation Latino Health Survey. Dependent variables were ever prayed for healing (yes/no), ever asked others to pray for healing (yes/no), considered important spiritual healing (very vs. somewhat or not important), and ever consulted a ‘curandero’ (folk healer in Latin America) (yes/no). The primary independent variables were feelings about the last time seeing a Doctor (confused by information given, or frustrated by lack of information) and perception of quality of medical care (excellent, good, fair or poor) within the past 12 months. Six percent of individuals reported that they had ever consulted a curandero, 60% prayed for healing, 49% asked others to pray for healing, and 69% considered spiritual healing as very important. In multivariable analyses, feeling confused was associated with increased odds of consulting a curandero (OR = 1.58; 95% CI, 1.02–2.45), praying for healing (OR = 1.30; 95% CI, 1.03–1.64), asking others to pray for healing (OR = 1.29; 95% CI, 1.03–1.62), and considering spiritual healing as very important (OR = 1.30; 95% CI, 1.01–1.66). Feeling frustrated by a lack of information was associated with asking others to pray for healing (OR = 1.29; 95% CI, 1.04–1.60). A better perception of quality of medical care was associated with lower odds of consulting a curandero (OR = 0.83; 95% CI, 0.70–0.98). Feelings about the medical encounter were associated with spirituality healing, praying for healing, and asking others to pray for healing. Feeling confused and perception of poor quality of medical care were associated with consulting a curandero

Association of KIR2DS1 and KIR2DS3 with fatal outcome in Ebola virus infection

Zaïre ebolavirus (ZEBOV) infection rapidly outruns the host's immunity and leads to death within a week. Fatal cases have been associated with an aberrant innate, proinflammatory immune response followed by a suppressed adaptive response leading to the rapid depletion of peripheral NK cells and lymphocytes. A critical role for NK cells has been suggested but not elucidated. In this genetic study, we investigated the association of KIR genotype with disease outcome by comparing genotypes of a Gabonese control population, IgG+ contacts, survivors, and fatalities of ZEBOV infection. We showed that the activating KIR2DS1 and KIR2DS3 genes associate with fatal outcome in Ebola virus infection. In addition, this study brings supplemental evidence in favor of the specificity of the IgG+ contact population. The outcome of fulminating Ebola virus infection could depend in part on the host's inherited KIR gene repertoire. This supports a key role for KIRs in disease susceptibility to infections

Aspergillus fumigatus Stimulates the NLRP3 Inflammasome through a Pathway Requiring ROS Production and the Syk Tyrosine Kinase

Invasive aspergillosis (IA) is a life-threatening disease that occurs in immunodepressed patients when infected with Aspergillus fumigatus. This fungus is the second most-common causative agent of fungal disease after Candida albicans. Nevertheless, much remains to be learned about the mechanisms by which A. fulmigatus activates the innate immune system. We investigated the inflammatory response to conidia and hyphae of A. fumigatus and specifically, their capacity to trigger activation of an inflammasome. Our results show that in contrast to conidia, hyphal fragments induce NLRP3 inflammasome assembly, caspase-1 activation and IL-1β release from a human monocyte cell line. The ability of Aspergillus hyphae to activate the NLRP3 inflammasome in the monocytes requires K+ efflux and ROS production. In addition, our data show that NLRP3 inflammasome activation as well as pro-IL-1β expression relies on the Syk tyrosine kinase, which is downstream from the pathogen recognition receptor Dectin-1, reinforcing the importance of Dectin-1 in the innate immune response against fungal infection. Furthermore, we show that treatment of monocytes with corticosteroids inhibits transcription of the gene encoding IL-1β. Thus, our data demonstrate that the innate immune response against A. fumigatus infection involves a two step activation process, with a first signal promoting expression and synthesis of pro-IL-1β; and a second signal, involving Syk-induced activation of the NLRP3 inflammasome and caspase-1, allowing processing and secretion of the mature cytokine