Recent advances in understanding Listeria monocytogenes infection: the importance of subcellular and physiological context.
Ontology highlight
ABSTRACT:
SUBMITTER: David DJV
PROVIDER: S-EPMC5516218 | biostudies-other | 2017
REPOSITORIES: biostudies-other
Similar Datasets
Project description:A number of significant challenges remain with regard to the diagnosis, treatment, and prevention of infections with Streptococcus pneumoniae (pneumococcus), which remains the most common bacterial cause of community-acquired pneumonia. Although this infection is documented to be extremely common in younger children and in older adults, the burden of pneumonia it causes is considerably underestimated, since the incidence statistics are derived largely from bacteremic infections, because they are easy to document, and yet the greater burden of pneumococcal pneumonias is non-invasive. It has been estimated that for every bacteremic pneumonia that is documented, three non-bacteremic infections occur. Management of these infections is potentially complicated by the increasing resistance of the isolates to the commonly used antibiotics. Furthermore, it is well recognized that despite advances in medical care, the mortality of bacteremic pneumococcal pneumonia has remained largely unchanged over the past 50 years and averages approximately 12%. Much recent research interest in the field of pneumococcal infections has focused on important virulence factors of the organism, on improved diagnostic and prognostication tools, on defining risk factors for death, on optimal treatment strategies involving both antibiotics and adjunctive therapies, and on disease prevention. It is hoped that through these endeavors the outlook of pneumococcal infections will be improved.
| S-EPMC4166932 | biostudies-literature
Project description:Complex mechanisms control the signaling of neurotrophins through p75 NTR and Trk receptors, allowing cellular responses that are highly context dependent, particularly in the nervous system and particularly with regard to the neurotrophin brain-derived neurotrophic factor (BDNF). Recent reports describe a variety of sophisticated regulatory mechanisms that contribute to such functional flexibility. Mechanisms described include regulation of trafficking of alternative BDNF transcripts, regulation of post-translational processing and secretion of BDNF, engagement of co-receptors that influence localization and signaling of p75 NTR and Trk receptors, and control of trafficking of receptors in the endocytic pathway and during anterograde and retrograde axonal transport.
| S-EPMC6758832 | biostudies-literature
Project description:ISG15 is primarily documented as an interferon-stimulated, ubiquitin-like protein (ubl), which has anti-viral activity. Although ISG15 was the founding member of the ubl protein family, very little is known about its function. We have found that ISG15 expression in non-phagocytic cells is dramatically induced upon Listeria infection and that surprisingly this induction can be Type I Interferon independent. Listeria-mediated ISG15 induction depends on the cytosolic surveillance pathway, which senses bacterial DNA and signals through STING, TBK1, IRF3 and IRF7. Most importantly, we observed that ISG15 expression restricts Listeria infection both in vitro and in vivo. We then made use of Stable Isotope Labeling in tissue culture (SILAC) to identify the ISGylated proteins that could be responsible for the ISG15-mediated protective effect. Our SILAC analysis revealed that overexpression of ISG15 leads to a striking ISGylation of integral membrane proteins of the endoplasmic reticulum and Golgi apparatus, which correlates with increased canonical secretion of cytokines. Taken together, our data reveal a previously uncharacterized signaling pathway that restricts Listeria infection and acts via ISGylation, reinforcing the view that ISG15 is a key component of the innate immune arsenal of the mammalian host.
2017-03-29 | MSV000080750 | MassIVE
Project description:Vitiligo, an acquired depigmentation disorder, manifests as white macules on the skin and can cause significant psychological stress and stigmatization. Recent advances have shed light on key components that drive disease onset and progression as well as therapeutic approaches. Vitiligo can be triggered by stress to the melanin pigment-producing cells of the skin, the melanocytes. The triggers, which range from sunburn to mechanical trauma and chemical exposures, ultimately cause an autoimmune response that targets melanocytes, driving progressive skin depigmentation. The most significant progress in our understanding of disease etiology has been made on three fronts: (1) identifying cellular responses to stress, including antioxidant pathways and the unfolded protein response (UPR), as key players in disease onset, (2) characterizing immune responses that target melanocytes and drive disease progression, and (3) identifying major susceptibility genes. The current model for vitiligo pathogenesis postulates that oxidative stress causes cellular disruptions, including interruption of protein maturation in the endoplasmic reticulum (ER), leading to the activation of the UPR and expression of UPR-regulated chemokines such as interleukin 6 (IL-6) and IL-8. These chemokines recruit immune components to the skin, causing melanocytes to be targeted for destruction. Oxidative stress can further increase melanocyte targeting by promoting antigen presentation. Two key components of the autoimmune response that promote disease progression are the interferon (IFN)-?/CXCL10 axis and IL-17-mediated responses. Several genome-wide association studies support a role for these pathways, with the antioxidant gene NRF2, UPR gene XBP1, and numerous immune-related genes including class I and class II major histocompatibility genes associated with a risk for developing vitiligo. Novel approaches to promote repigmentation in vitiligo are being investigated and may yield effective, long-lasting therapies.
| S-EPMC5017284 | biostudies-other
Project description:The definition of cholangiocarcinoma (CCA) encompasses all tumors originating in the epithelium of the bile ducts, including the intrahepatic bile ducts (ICCA) and extrahepatic bile ducts (ECCA). The incidence of ICCA and ECCA has increased in the last few decades, and molecular advances in both entities have brought understanding of their differences and allowed treatment advances aimed at personalized therapy. In this review, we discuss recent progress in the molecular landscape of CCAs, emerging treatment biomarker-guided strategies, and future insights into the management of advanced disease.
| S-EPMC7886064 | biostudies-literature
Project description:ISG15 is an interferon-stimulated, linear di-ubiquitin-like protein, with anti-viral activity. The role of ISG15 during bacterial infection remains elusive. We show that ISG15 expression in nonphagocytic cells is dramatically induced upon Listeria infection. Surprisingly this induction can be type I interferon independent and depends on the cytosolic surveillance pathway, which senses bacterial DNA and signals through STING, TBK1, IRF3 and IRF7. Most importantly, we observed that ISG15 expression restricts Listeria infection in vitro and in vivo. We made use of stable isotope labeling in tissue culture (SILAC) to identify ISGylated proteins that could be responsible for the protective effect. Strikingly, infection or overexpression of ISG15 leads to ISGylation of ER and Golgi proteins, which correlates with increased secretion of cytokines known to counteract infection. Together, our data reveal a previously uncharacterized ISG15-dependent restriction of Listeria infection, reinforcing the view that ISG15 is a key component of the innate immune response.
| S-EPMC4530601 | biostudies-literature
Project description:Signal transducer and activator of transcription 1 (Stat1) is a key player in responses to interferons (IFN). Mutations of Stat1 cause severe immune deficiencies in humans and mice. Here we investigate the importance of Stat1 signaling for the innate and secondary immune response to the intracellular bacterial pathogen Listeria monocytogenes (Lm). Cell type-restricted ablation of the Stat1 gene in naïve animals revealed unique roles in three cell types: macrophage Stat1 signaling protected against lethal Lm infection, whereas Stat1 ablation in dendritic cells (DC) did not affect survival. T lymphocyte Stat1 reduced survival. Type I IFN (IFN-I) signaling in T lymphocytes reportedly weakens innate resistance to Lm. Surprisingly, the effect of Stat1 signaling was much more pronounced, indicating a contribution of Stat1 to pathways other than the IFN-I pathway. In stark contrast, Stat1 activity in both DC and T cells contributed positively to secondary immune responses against Lm in immunized animals, while macrophage Stat1 was dispensable. Our findings provide the first genetic evidence that Stat1 signaling in different cell types produces antagonistic effects on innate protection against Lm that are obscured in mice with complete Stat1 deficiency. They further demonstrate a drastic change in the cell type-dependent Stat1 requirement for memory responses to Lm infection.
| S-EPMC3375314 | biostudies-literature
Project description:Clostridium difficile epidemiology has changed in recent years, with the emergence of highly virulent types associated with severe infections, high rates of recurrences and mortality. Antibiotic resistance plays an important role in driving these epidemiological changes and the emergence of new types. While clindamycin resistance was driving historical endemic types, new types are associated with resistance to fluoroquinolones. Furthermore, resistance to multiple antibiotics is a common feature of the newly emergent strains and, in general, of many epidemic isolates. A reduced susceptibility to antibiotics used for C. difficile infection (CDI) treatment, in particular to metronidazole, has recently been described in several studies. Furthermore, an increased number of strains show resistance to rifamycins, used for the treatment of relapsing CDI. Several mechanisms of resistance have been identified in C. difficile, including acquisition of genetic elements and alterations of the antibiotic target sites. The C. difficile genome contains a plethora of mobile genetic elements, many of them involved in antibiotic resistance. Transfer of genetic elements among C. difficile strains or between C. difficile and other bacterial species can occur through different mechanisms that facilitate their spread. Investigations of the fitness cost in C. difficile indicate that both genetic elements and mutations in the molecular targets of antibiotics can be maintained regardless of the burden imposed on fitness, suggesting that resistances may persist in the C. difficile population also in absence of antibiotic selective pressure. The rapid evolution of antibiotic resistance and its composite nature complicate strategies in the treatment and prevention of CDI. The rapid identification of new phenotypic and genotypic traits, the implementation of effective antimicrobial stewardship and infection control programs, and the development of alternative therapies are needed to prevent and contain the spread of resistance and to ensure an efficacious therapy for CDI.
| S-EPMC4735502 | biostudies-literature
Project description:Exonic circular RNAs (circRNAs) have been discovered in all kingdoms of life. In many cases, the details of circRNA function and their involvement in cellular processes and diseases are not yet fully understood. However, the past few years have seen significant developments in bioinformatics and in experimental protocols that advance the ongoing research in this still-emerging field. Sophisticated methods for circRNA generation in vitro and in vivo have been developed, allowing model studies into circRNA function and application. We here review the ongoing circRNA research, giving special attention to recent progress in the field.
| S-EPMC7324948 | biostudies-literature
Project description:By definition, congenital myopathy typically presents with skeletal muscle weakness and hypotonia at birth. Traditionally, congenital myopathy subtypes have been predominantly distinguished on the basis of the pathological hallmarks present on skeletal muscle biopsies. Many genes cause congenital myopathies when mutated, and a burst of new causative genes have been identified because of advances in gene sequencing technology. Recent discoveries include extending the disease phenotypes associated with previously identified genes and determining that genes formerly known to cause only dominant disease can also cause recessive disease. The more recently identified congenital myopathy genes account for only a small proportion of patients. Thus, the congenital myopathy genes remaining to be discovered are predicted to be extremely rare causes of disease, which greatly hampers their identification. Significant progress in the provision of molecular diagnoses brings important information and value to patients and their families, such as possible disease prognosis, better disease management, and informed reproductive choice, including carrier screening of parents. Additionally, from accurate genetic knowledge, rational treatment options can be hypothesised and subsequently evaluated in vitro and in animal models. A wide range of potential congenital myopathy therapies have been investigated on the basis of improved understanding of disease pathomechanisms, and some therapies are in clinical trials. Although large hurdles remain, promise exists for translating treatment benefits from preclinical models to patients with congenital myopathy, including harnessing proven successes for other genetic diseases.
| S-EPMC6290972 | biostudies-literature