Person: Vyas, Jatin
Loading...
Email Address
AA Acceptance Date
Birth Date
Research Projects
Organizational Units
Job Title
Last Name
Vyas
First Name
Jatin
Name
Vyas, Jatin
10 results
Search Results
Now showing 1 - 10 of 10
Publication The Role of Autophagy-Related Proteins in Candida albicans Infections(MDPI, 2016) Tam, Jenny; Mansour, Michael; Acharya, Mridu; Sokolovska, Anna; Timmons, Allison K.; Lacy-Hulbert, Adam; Vyas, JatinAutophagy plays an important role in maintaining cell homeostasis by providing nutrients during periods of starvation and removing damaged organelles from the cytoplasm. A marker in the autophagic process is the reversible conjugation of LC3, a membrane scaffolding protein, to double membrane autophagosomes. Recently, a role for LC3 in the elimination of pathogenic bacteria and fungi, including Candida albicans (C. albicans), was demonstrated, but these organisms reside in single membrane phagosomes. This process is distinct from autophagy and is termed LC3-associated phagocytosis (LAP). This review will detail the hallmarks of LAP that distinguish it from classical autophagy and review the role of autophagy proteins in host response to C. albicans and other pathogenic fungi.Publication Erratum to: Modulatory role of vitamin A on the Candida albicans-induced immune response in human monocytes(Springer Berlin Heidelberg, 2014) Klassert, Tilman E.; Hanisch, Anja; Bräuer, Julia; Klaile, Esther; Heyl, Kerstin A.; Mansour, Michael; Tam, Jenny; Vyas, Jatin; Slevogt, HortensePublication Modulatory role of vitamin A on the Candida albicans-induced immune response in human monocytes(Springer Berlin Heidelberg, 2014) Klassert, Tilman E.; Hanisch, Anja; Bräuer, Julia; Klaile, Esther; Heyl, Kerstin A.; Mansour, Michael M.; Tam, Jenny; Vyas, Jatin; Slevogt, HortenseBeyond its well-documented role in reproduction, embryogenesis and maintenance of body tissues, vitamin A has attracted considerable attention due to its immunomodulatory effects on both the innate and the adaptive immune responses. In infectious diseases, vitamin A has been shown to have a host-protective effect in infections of bacterial, viral or protozoan origin. Nevertheless, its impact in fungal infections remains unknown. Meanwhile, the frequency of invasive mycoses keeps on growing, with Candida albicans being the major opportunistic fungal pathogen and associated with high mortality. In the present work, we explored the impact of all-trans retinoic acid (atRA), the most active metabolite of vitamin A, on the innate immune response against C.albicans in human monocytes. Our results show a strong immunomodulatory role for atRA, leading to a significant down-regulation of the fungi-induced expression and secretion of the pro-inflammatory cytokines TNFα, IL6 and IL12. Moreover, atRA significantly suppressed the expression of Dectin-1, a major fungal pattern recognition receptor, as well as the Dectin-1-dependent cytokine production. Both RAR-dependent and RAR-independent mechanisms seem to play a role in the atRA-mediated immunomodulation. Our findings open a new direction to elucidate the role of vitamin A on the immune function during fungal infections. Electronic supplementary material The online version of this article (doi:10.1007/s00430-014-0351-4) contains supplementary material, which is available to authorized users.Publication Dectin-1 Activation Controls Maturation of β-1,3-Glucan-containing Phagosomes(American Society for Biochemistry & Molecular Biology (ASBMB), 2013) Mansour, Michael; Tam, Jenny; Khan, Nida S.; Seward, Michael; Davids, Peter J.; Puranam, Sravanthi; Sokolovska, Anna; Sykes, David; Dagher, Zeina; Becker, Christine; Tanne, Antoine; Reedy, Jennifer; Stuart, Lynda M.; Vyas, JatinBackground: Dectin-1 is able to recognize and phagocytose the fungal carbohydrate, β-1,3-glucan, but its contribution to phagosomal maturation has not been explored. Results: Dectin-1-dependent Syk activation promotes phagolysosomal fusion and acidification. Conclusion: Dectin-1-dependent Syk-activation permits egress of early phagosomes to mature phagolysosomes. Significance: The surface recognition receptor, Dectin-1 shapes anti-fungal responses by controlling fungal phagosome maturation.Publication Serial Procalcitonin Levels Correlate with Microbial Etiology in Hospitalized Patients with Pneumonia(Oxford University Press, 2017) Ankomah, Pierre; McCluskey, Suzanne; Abers, Michael; Bearnot, Benjamin; Patel, Shreya; Schuetz, Philipp; Chiappa, Vic; Lewandrowski, Kent; Vyas, Jatin; Mansour, MichaelAbstract Background: Procalcitonin (PCT) is a biomarker that is finding increasing diagnostic and prognostic utility in lower respiratory infections. It remains unclear, however, whether it can be helpful in predicting the bacterial etiology of pneumonia, with a view to informing antibiotic choice and duration. This study examines the relationship between serial PCT measurements and microbial etiology in patients hospitalized for pneumonia to determine whether changes in PCT levels provide discriminatory information on microbial etiology. Methods: We performed a subgroup analysis of data from a prospective cohort study of 505 patients admitted to a tertiary care center with findings concerning for pneumonia. Microbial etiology of pneumonia was determined from high quality respiratory samples, blood cultures or other relevant diagnostic tests according to standard protocols. Procalcitonin levels were measured serially during the first four days of hospitalization. We compared procalcitonin levels between different bacterial etiologies over the first four days of admission, using the Mann–Whitney-U test to assess for statistical significance. Results: Out of 505 patients, the diagnosis of pneumonia was adjudicated in 317, and bacterial etiology determined in 62 cases. The predominant pathogens were Staphylococcus aureus (N = 18), Streptococcus pneumoniae (N = 6), Pseudomonas aeruginosa (N = 11) and Haemophilus influenza (N = 5). Admission levels of PCT were lowest in Pseudomonas infections and highest in pneumococcal infections, though not reaching statistical significance. On hospital days two and three, pneumococcal procalcitonin levels were significantly higher than all other etiologies, but on day four, there was no statistically significant difference in PCT values for different microbial etiologies. Conclusion: Serial procalcitonin levels during the early course of bacterial pneumonia reveal a difference between pneumococcal and other bacterial etiologies, and may have an adjunct role in guiding antibiotic choice and duration. Disclosures All authors: No reported disclosures.Publication Risks Associated With Lentiviral Vector Exposures and Prevention Strategies(Lippincott Williams & Wilkins, 2016) Schlimgen, Ryan; Howard, John; Wooley, Dawn; Thompson, Maureen; Baden, Lindsey; Yang, Otto O.; Christiani, David; Mostoslavsky, Gustavo; Diamond, David; Duane, Elizabeth Gilman; Byers, Karen; Winters, Thomas; Gelfand, Jeffrey; Fujimoto, Gary; Hudson, T. Warner; Vyas, JatinLentiviral vectors (LVVs) are powerful genetic tools that are being used with greater frequency in biomedical laboratories and clinical trials. Adverse events reported from initial clinical studies provide a basis for risk assessment of occupational exposures, yet many questions remain about the potential harm that LVVs may cause. We review those risks and provide a framework for principal investigators, Institutional Biosafety Committees, and occupational health professionals to assess and communicate the risks of exposure to staff. We also provide recommendations to federal research and regulatory agencies for tracking LVV exposures to evaluate long-term outcomes. U.S. Food and Drug Administration approved antiviral drugs for HIV have theoretical benefits in LVV exposures, although evidence to support their use is currently limited. If treatment is appropriate, we recommend a 7-day treatment with an integrase inhibitor with or without a reverse transcriptase inhibitor within 72 hours of exposure.Publication A Critical Reappraisal of Prolonged Neutropenia as a Risk Factor for Invasive Pulmonary Aspergillosis(Oxford University Press, 2016) Abers, Michael; Ghebremichael, Musie; Timmons, Allison K.; Warren, H.; Poznansky, Mark; Vyas, JatinProlonged neutropenia is generally thought to be the major factor for invasive pulmonary aspergillosis (IPA). In the present study, we characterize the frequency, severity, and duration of neutropenia that immediately precedes IPA. Prolonged neutropenia was identified in only one third of all IPA cases and occurred exclusively in hematologic patients.Publication αv Integrins combine with LC3 and atg5 to regulate Toll-like receptor signalling in B cells(Nature Publishing Group, 2016) Acharya, Mridu; Sokolovska, Anna; Tam, Jenny; Conway, Kara L.; Stefani, Caroline; Raso, Fiona; Mukhopadhyay, Subhankar; Feliu, Marianela; Paul, Elahna; Savill, John; Hynes, Richard O.; Xavier, Ramnik; Vyas, Jatin; Stuart, Lynda M.; Lacy-Hulbert, AdamIntegrin signalling triggers cytoskeletal rearrangements, including endocytosis and exocytosis of integrins and other membrane proteins. In addition to recycling integrins, this trafficking can also regulate intracellular signalling pathways. Here we describe a role for αv integrins in regulating Toll-like receptor (TLR) signalling by modulating intracellular trafficking. We show that deletion of αv or β3 causes increased B-cell responses to TLR stimulation in vitro, and αv-conditional knockout mice have elevated antibody responses to TLR-ligand-associated antigens. αv regulates TLR signalling by promoting recruitment of the autophagy component LC3 (microtubule-associated proteins 1 light chain 3) to TLR-containing endosomes, which is essential for progression from NF-κB to IRF signalling, and ultimately for traffic to lysosomes where signalling is terminated. Disruption of LC3 recruitment leads to prolonged NF-κB signalling and increased B-cell proliferation and antibody production. This work identifies a previously unrecognized role for αv and the autophagy components LC3 and atg5 in regulating TLR signalling and B-cell immunity.Publication Control and Manipulation of Pathogens with an Optical Trap for Live Cell Imaging of Intercellular Interactions(Public Library of Science, 2010) Tam, Jenny; Castro, Carlos E.; Heath, Robert John William; Cardenas, Michael L.; Xavier, Ramnik; Lang, Matthew J.; Vyas, JatinThe application of live cell imaging allows direct visualization of the dynamic interactions between cells of the immune system. Some preliminary observations challenge long-held beliefs about immune responses to microorganisms; however, the lack of spatial and temporal control between the phagocytic cell and microbe has rendered focused observations into the initial interactions of host response to pathogens difficult. This paper outlines a method that advances live cell imaging by integrating a spinning disk confocal microscope with an optical trap, also known as an optical tweezer, in order to provide exquisite spatial and temporal control of pathogenic organisms and place them in proximity to host cells, as determined by the operator. Polymeric beads and live, pathogenic organisms (Candida albicans and Aspergillus fumigatus) were optically trapped using non-destructive forces and moved adjacent to living cells, which subsequently phagocytosed the trapped particle. High resolution, transmitted light and fluorescence-based movies established the ability to observe early events of phagocytosis in living cells. To demonstrate the broad applicability of this method to immunological studies, anti-CD3 polymeric beads were also trapped and manipulated to form synapses with T cells in vivo, and time-lapse imaging of synapse formation was also obtained. By providing a method to exert fine control of live pathogens with respect to immune cells, cellular interactions can be captured by fluorescence microscopy with minimal perturbation to cells and can yield powerful insight into early responses of innate and adaptive immunity.Publication Corticosteroid Use Following the Onset of Invasive Aspergillosis is Associated with Increased Mortality: A Propensity Score-Matched Study(Oxford University Press, 2017) Abers, Michael; Vyas, JatinAbstract Background: The safety of corticosteroid use (CSU) during active infection is controversial. In the invasive aspergillosis (IA) literature, CSU is typically defined using the time period prior to IA onset. Clinicians caring for patients with IA are unable to control prior CSU. The more clinically relevant question is whether CSU after IA onset is harmful. Methods: Patients hospitalized at our institution from 2004 to 2014 with IA were retrospectively identified. CSU, defined as the average daily prednisone equivalent dose during the 7-day period following IA onset, was calculated for each patient. A CSU cut-off of 7.5mg was used to assign patients to treatment (>7.5mg) or control (<7.5mg, including no CSU) groups. A propensity score (PS) was generated to predict group assignment. Nearest neighbor matching was performed with a caliper width of 0.2. A Cox proportional hazards model was used to assess survival 6 weeks after IA onset. Results: PS matching generated 61 matched pairs (122 patients). Baseline characteristics did not differ significantly between groups (Table). CSU was associated with increased mortality (PS adjusted hazard ratio [HR] 2.91, 95% CI 1.32–6.40). In the CSU group, a trend towards lower mortality was noted if corticosteroid dose was tapered to 7.5mg/day (HR 0.68, 95% CI 0.46–1.02). Conclusion: CSU after IA onset is associated with increased mortality. In IA patients with CSU, efforts to reduce corticosteroid dose may be beneficial. Table: Propensity matched patients at IA Onset CSU (n = 61) Control (n = 61) P Age, years 57.6 (49.2–65.9) 53.2 (42.5–63.2) .27 Male 59.0% (36/61) 54.1% (33/61) .72 CSU >7.5mg prior to IA 78.7% (48/61) 70.5% (43/61) .41 Leukemia 52.5% (32/61) 49.2% (30/61) .86 Allogeneic bone marrow transplant 26.2% (16/61) 29.5% (18/61) .84 Graft vs. host disease 3.3% (2/61) 11.5% (7/61) .16 Neutropenia 48.3% (28/58) 42.9% (24/56) .58 Solid organ transplant 11.5% (7/61) 6.6% (4/61) .53 Obstructive lung disease 21.3% (13/61) 24.6% (15/61) .83 Diabetes mellitus 26.2% (16/61) 29.5% (18/61) .84 Pulmonary IA 94.8% (55/58) 94.9% (56/59) .99 Coinfection 23.0% (14/61) 21.3% (13/61) .99 Data presented as median (interquartile range) or % (n with feature/n with data available) Figure. Kaplan–Meier curves comparing 6-week survival Disclosures All authors: No reported disclosures.