Dual requirement of cytokine and activation receptor triggering for cytotoxic control of murine cytomegalovirus by NK cells

Natural killer (NK) cells play a critical role in controlling murine cytomegalovirus (MCMV) and can mediate both cytokine production and direct cytotoxicity. The NK cell activation receptor, Ly49H, is responsible for genetic resistance to MCMV in C57BL/6 mice. Recognition of the viral m157 protein by Ly49H is sufficient for effective control of MCMV infection. Additionally, during the host response to infection, distinct immune and non-immune cells elaborate a variety of pleiotropic cytokines which have the potential to impact viral pathogenesis, NK cells, and other immune functions, both directly and indirectly. While the effects of various immune deficiencies have been examined for general antiviral phenotypes, their direct effects on Ly49H-dependent MCMV control are poorly understood. To specifically interrogate Ly49H-dependent functions, herein we employed an in vivo viral competition approach to show Ly49H-dependent MCMV control is specifically mediated through cytotoxicity but not IFNγ production. Whereas m157 induced Ly49H-dependent degranulation, efficient cytotoxicity also required either IL-12 or type I interferon (IFN-I) which acted directly on NK cells to produce granzyme B. These studies demonstrate that both of these distinct NK cell-intrinsic mechanisms are integrated for optimal viral control by NK cells

Information systems for innovation: A comparative analysis of maturity models' characteristics

Nowadays, virtually all industries are impacted by the digitalization of business enabled by information and communication technologies. Consequently, it is a major challenge to any business to increase its ability to innovate through information systems. However the effort and the investments of companies are extremely varied, they do not have the same level of maturity with respect to their innovation strategy. While some highly mature use effective approaches, others still act as novices or use inadequate practices. The question raised in this paper is how to evaluate the level of maturity of an organization with respect to information systems based innovation. Also, the question concerns the identification of the salient features of ICT centred innovation maturity models. Taking these issues into account, the paper makes the following contributions: (i) a review of sixteen innovation maturity models collected from the research and the practitioners community, gathering facts about the models and about their effectiveness; (ii) a comparative analysis of these models

Airway Secretory microRNAome Changes during Rhinovirus Infection in Early Childhood

<div><p>Background</p><p>Innate immune responses are fine-tuned by small noncoding RNA molecules termed microRNAs (miRs) that modify gene expression in response to the environment. During acute infections, miRs can be secreted in extracellular vesicles (EV) to facilitate cell-to-cell genetic communication. The purpose of this study was to characterize the baseline population of miRs secreted in EVs in the airways of young children (airway secretory microRNAome) and examine the changes during rhinovirus (RV) infection, the most common cause of asthma exacerbations and the most important early risk factor for the development of asthma beyond childhood.</p><p>Methods</p><p>Nasal airway secretions were obtained from children (≤3 yrs. old) during PCR-confirmed RV infections (n = 10) and age-matched controls (n = 10). Nasal EVs were isolated with polymer-based precipitation and global miR profiles generated using NanoString microarrays. We validated our <i>in vivo</i> airway secretory miR data in an <i>in vitro</i> airway epithelium model using apical secretions from primary human bronchial epithelial cells (HBEC) differentiated at air-liquid interface (ALI). Bioinformatics tools were used to determine the unified (nasal and bronchial) signature airway secretory miRNAome and changes during RV infection in children.</p><p>Results</p><p>Multiscale analysis identified four signature miRs comprising the baseline airway secretory miRNAome: <i>hsa-miR-630</i>, <i>hsa-miR-302d-3p</i>, <i>hsa- miR-320e</i>, <i>hsa-miR-612</i>. We identified <i>hsa-miR-155</i> as the main change in the baseline miRNAome during RV infection in young children. We investigated the potential biological relevance of the airway secretion of <i>hsa-mir-155</i> using <i>in silico</i> models derived from gene datasets of experimental <i>in vivo</i> human RV infection. These analyses confirmed that <i>hsa-miR-155</i> targetome is an overrepresented pathway in the upper airways of individuals infected with RV.</p><p>Conclusions</p><p>Comparative analysis of the airway secretory microRNAome in children indicates that RV infection is associated with airway secretion of EVs containing miR-155, which is predicted <i>in silico</i> to regulate antiviral immunity. Further characterization of the airway secretory microRNAome during health and disease may lead to completely new strategies to treat and monitor respiratory conditions in all ages.</p></div

Natural killer cell memory in infection, inflammation and cancer

Immunological memory can be defined as a quantitatively and qualitatively enhanced immune response upon rechallenge. For natural killer (NK) cells, two main types of memory exist. First, similarly to T cells and B cells, NK cells can exert immunological memory after encounters with stimuli such as haptens or viruses, resulting in the generation of antigen-specific memory NK cells. Second, NK cells can remember inflammatory cytokine milieus that imprint long-lasting non-antigen-specific NK cell effector function. The basic concepts derived from studying NK cell memory provide new insights about innate immunity and could lead to novel strategies to improve treatments for infectious diseases and cancer