Background. Nosocomial infections with Klebsiella pneumoniae are a frequent cause of Gram-negative bacterial sepsis. To understand the functioning host innate immune components in this disorder, we examined previously uninvestigated role C-type lectin receptor Mincle pneumonic sepsis caused by K. pneumoniae. Methods. Disease progression wild-type and Mincle−/− mice undergoing pulmonary infection was compared. Results. Whereas infected sublethal dose bacteria could resolve clearance regulated...

Neutrophils are the first infiltrating cell type essential for combating pneumoseptic infections by bacterial pathogens including Klebsiella pneumoniae (KPn). Following an infection or injury, removal of apoptotic infiltrates via a highly regulated process called efferocytosis is required restoration homeostasis, but little known regarding effect on this process. Here we demonstrate that KPn impedes efferocytic uptake neutrophils in-vitro and in-vivo in lungs macrophages. This impaired...

Highlights•TRPC1 mediates sterile or infection-induced Ca2+ influx and M1 phenotype in macrophages•ORAI1 the basal macrophages•In patients with SIRS, TRPC1 level correlates inflammatory mediators macrophagesSummaryMacrophage plasticity is essential for innate immunity, but in-depth signaling mechanism(s) regulating their functional phenotypes are ill-defined. Here we report that interferon (IFN) γ priming of naive macrophages induces store-mediated entry inhibition impairs polarization to...

Neutrophil extracellular traps (NETs) constitute antimicrobial function of neutrophils but have also been linked to perpetuation inflammation. Despite this evident physiological relevance, mechanistic understanding NET formation is poor. In study, we examined the mechanism by which Mincle, a C-type lectin receptor, regulates formation.NET formation, reactive oxygen species, autophagy activation and intracellular signaling pathways were analyzed in Mincle-sufficient -deficient stimulated...

C-type lectin receptors (CLRs), the carbohydrate-recognizing molecules, orchestrate host immune response in homeostasis and inflammation. In present study we examined function of macrophage galactose-type lectin-1 (MGL1), a mammalian CLR, pneumonic sepsis, deadly disorder frequently associated with nonresolving hyperinflammation. murine model sepsis using pulmonary infection Klebsiella pneumoniae, expression MGL1 was upregulated lungs K. pneumoniae-infected mice, deficiency this CLR...

Gammaherpesviruses are ubiquitous viruses that establish lifelong infections. Importantly, these associated with numerous cancers and lymphoproliferative diseases. While risk factors for developing gammaherpesvirus-driven poorly understood, it is clear elevated viral reactivation from latency often precedes oncogenesis. Here, we demonstrate the liver X receptor alpha isoform (LXRα) restricts gammaherpesvirus in an anatomic-site-specific manner. We have previously demonstrated deficiency of...

Gammaherpesviruses are ubiquitous pathogens that associated with B cell lymphomas. In the early stages of chronic infection, these viruses infect naive cells and subsequently usurp differentiation process through germinal center response to ensure latent infection long-lived memory cells. A unique feature gammaherpesvirus is a robust irrelevant, virus-nonspecific reactivities against self-antigens antigens other species. contrast, protective, virus-specific humoral responses do not reach...

Gammaherpesviruses establish lifelong infection and are associated with a variety of cancers, including B cell lymphomas. These viruses manipulate the differentiation process to in memory cells. Specifically, gammaherpesviruses infect naive cells promote entry both infected uninfected into germinal centers, where virus usurps rapid proliferation center exponentially increase its cellular latent reservoir. In addition facilitating establishment infection, thought be target viral...

Gammaherpesviruses are ubiquitous pathogens that establish lifelong infections and associated with a variety of malignancies, including lymphomas. Interferon regulatory factor 7 (IRF-7) is an innate immune transcription restricts acute replication diverse viruses, murine gammaherpesvirus 68 (MHV68). Importantly, very little known about the role IRF-7 during chronic virus infections. In this study, we demonstrate attenuates infection by restricting establishment latency in peritoneal cavity...

Gammaherpesviruses establish lifelong infection in over 95% of all adults and are associated with B cell lymphomas. The virus’s manipulation the germinal center response differentiation to is thought also precipitate malignant transformation, through a mechanism that remains poorly understood. host transcription factor IRF-1, well-established tumor suppressor, selectively attenuates MHV68-driven response, phenotype we originally hypothesized occur cell-intrinsic manner. In contrast, testing,...

Gammaherpesviruses establish lifelong infection in a majority of adults worldwide and are associated with number malignancies, including B cell lymphomas. These viruses infect naive cells manipulate differentiation to achieve memory cells. The germinal center stage is important as both an amplifier the viral latent reservoir target malignant transformation. In this study, we demonstrate that expression tyrosine phosphatase SHP1, negative regulator normally limits activation proliferation...

Gammaherpesviruses establish lifelong infections and are associated with B cell lymphomas. Murine gammaherpesvirus 68 (MHV68) infects epithelial myeloid cells during acute infection, subsequent passage of the virus to cells, where physiological differentiation is usurped ensure establishment a chronic latent reservoir. Interferons (IFNs) represent major antiviral defense system that engages transcriptional factor STAT1 attenuate diverse viral infections, including those gammaherpesviruses....

Gammaherpesviruses, such as human Epstein-Barr virus (EBV) and murine gammaherpesvirus 68 (MHV68), are species-specific, ubiquitous pathogens that associated with multiple cancers, including B cell lymphomas. These viruses have a natural tropism for cells usurp differentiation to drive unique robust polyclonal germinal center response establish long-term latent reservoir in memory cells. The driven by infection increases the risk transformation. Unsurprisingly, many cancers derived from or...

Gammaherpesviruses are ubiquitous pathogens that establish lifelong infections and associated with several malignancies, including B cell lymphomas. Uniquely, these viruses manipulate differentiation to long-term latency in memory cells. This study focuses on the interaction between gammaherpesviruses interferon regulatory factor 3 (IRF-3), a ubiquitously expressed transcription multiple direct target genes, beta (IFN-β), type I IFN. IRF-3 attenuates acute replication of plethora viruses,...

Gammaherpesviruses are ubiquitous pathogens that establish lifelong infection and associated with B cell lymphomas. To chronic infection, these viruses usurp differentiation drive a robust germinal center response to expand the latent viral reservoir gain access memory cells. Germinal cells, while important for establishment of also thought be target transformation. The host factors impact gammaherpesvirus-driven not clearly defined. We show global expression antiviral tumor suppressor...

Gammaherpesviruses establish lifelong infections in most vertebrate species, including humans and rodents, are associated with cancers, B cell lymphomas. While type I II interferon (IFN) systems of the host critical for control acute chronic gammaherpesvirus infection, type-specific role(s) IFN signaling during infection is poorly understood often masked by profoundly altered viral pathogenesis hosts global deficiencies. STAT1 a effector all classical responses along its involvement other...

Abstract Purpose of Review Gammaherpesviruses constitute the chief virus family that is capable exhibiting true latency. Latency allows viral genome to override host immune responses and persist despite unfavorable conditions. Due species specificity gammaherpesviruses, murine gammaherpesvirus 68 (MHV68), presents by far most advanced system for analyzing latency impact response in an intact host. Recent Findings publications show MHV68 utilizes components promote establishment Further,...

Abstract “Neutrophil extracellular traps (NETs) constitute antimicrobial function of neutrophils but have also been linked to perpetuation inflammation. Despite this evident physiological relevance, mechanistic understanding NET formation is poor. In the current study we examined mechanism by which Mincle, a C-type lectin receptor, regulates formation. We found that Mincle mediates in response several activation stimuli in-vitro and in-vivo during pneumoseptic infection with Klebsiella...

Gammaherpesviruses infect most vertebrate species and are associated with B cell lymphomas. Manipulation of differentiation is critical for natural infection lymphomagenesis driven by gammaherpesviruses. Specifically, human Epstein-Barr virus (EBV) murine gammaherpesvirus 68 (MHV68) drive infected naive cells into the germinal center to achieve exponential increase in latent viral reservoir during establishment chronic infection. Infected also target lymphomagenesis, as EBV-positive...

Abstract Lower respiratory tract infection with bacteria can lead to sepsis development, a complex immune disorder systemic hyperinflammation. There are currently no effective therapies for sepsis. To understand the function of specific pulmonary components in regulation responses this disorder, we utilize an acute bacterial model Klebsiella pneumoniae (KPn). Nosocomial infections opportunistic pathogen account 5-20% Gram-negative cases. C-type lectin receptors (CLRs), expressed mainly by...

Abstract Efficient clearance of invading pathogen and the infiltrating cells by phagocytic are two key events that required for successful elimination a pathological insult. Clearance is usually achieved phagocytosis dead cleared process called efferocytosis. While there substantial information on various strategies employed number pathogens to subvert phagocytosis, our knowledge about inhibition efferocytosis microbes extremely limited. In regard, we observed that, polymorphonuclear (PMNs)...