ORCID Profile
0000-0002-3104-2823
Current Organisation
University of Tennessee Health Science Center
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Publisher: Elsevier BV
Date: 02-2019
Publisher: Elsevier BV
Date: 09-2016
Publisher: Hindawi Limited
Date: 2017
DOI: 10.1155/2017/8903982
Abstract: In asthmatic airways, repeated epithelial damage and repair occur. No current therapy directly targets this process. We aimed to determine the effects of mannan derived from S. cerevisiae (SC-MN) on airway epithelial wound repair, in vitro . The presence of functional mannose receptors in bronchial epithelial cells was shown by endocytosis of colloidal gold-Man BSA via clathrin-coated pits in 16HBE cells. In primary normal human bronchial epithelial cells (NHBEC), SC-MN significantly facilitated wound closure. Treatment with SC-MN stimulated cell spreading as indicated by a significant increase in the average lamellipodial width of wound edge 16HBE cells. In addition, NHBEC treated with SC-MN showed increased expression and activation of Krüppel-like factors (KLFs) 4 and 5, transcription factors important in epithelial cell survival and regulation of epithelial-mesenchymal transition. We conclude that SC-MN facilitates wound repair in human bronchial epithelium, involving mannose receptors.
Publisher: Elsevier BV
Date: 12-2017
Publisher: Springer Science and Business Media LLC
Date: 04-05-2018
DOI: 10.1038/S41598-018-25321-Y
Abstract: Asthma is characterized by inflammation and architectural changes in the lungs. A number of immune cells and mediators are recognized as initiators of asthma, although therapeutics based on these are not always effective. The multifaceted nature of this syndrome necessitate continued exploration of immunomodulators that may play a role in pathogenesis. We investigated the role of resistin-like molecule-beta (RELM-β), a gut antibacterial, in the development and pathogenesis of Aspergillus -induced allergic airways disease. Age and gender matched C57BL/6J and Retnlb −/− mice rendered allergic to Aspergillus fumigatus were used to measure canonical markers of allergic asthma at early and late time points. Inflammatory cells in airways were similar, although Retnlb −/− mice had reduced tissue inflammation. The absence of RELM-β elevated serum IgA and pro-inflammatory cytokines in the lungs at homeostasis. Markers of chronic disease including goblet cell numbers, Muc genes, airway wall remodelling, and hyperresponsiveness were greater in the absence RELM-β. Specific inflammatory mediators important in antimicrobial defence in allergic asthma were also increased in the absence of RELM-β. These data suggest that while characteristics of allergic asthma develop in the absence of RELM-β, that RELM-β may reduce the development of chronic markers of allergic airways disease.
Publisher: Hindawi Limited
Date: 2017
DOI: 10.1155/2017/3432701
Abstract: One of the unmet needs for asthma management is a new therapeutic agent with both anti-inflammatory and anti-smooth muscle (ASM) remodeling effects. The mannose receptor (MR) family plays an important role in allergen uptake and processing of major allergens Der p 1 and Fel d 1. We have previously reported that ASM cells express a mannose receptor (ASM-MR) and that mannan derived from Saccharomyces cerevisiae (SC-MN) inhibits mannosyl-rich lysosomal hydrolase-induced bovine ASM cell proliferation. Using a humanized transgenic mouse strain (huASM-MRC2) expressing the human MRC2 receptor in a SM tissue-specific manner, we have demonstrated that ASM hyperplasia/hypertrophy can occur as early as 15 days after allergen challenge in this mouse model and this phenomenon is preventable with SC-MN treatment. This proof-of-concept study would facilitate future development of a potential asthma therapeutic agent with dual function of anti-inflammatory and anti-smooth muscle remodeling effects.
Publisher: Hindawi Limited
Date: 2018
DOI: 10.1155/2018/3298378
Abstract: Severe asthma with fungal sensitization predominates in the population suffering from allergic asthma, to which there is no cure. While corticosteroids are the mainstay in current treatment, other means of controlling inflammation may be beneficial. Herein, we hypothesized that mannan from Saccharomyces cerevisiae would d en the characteristics of fungal allergic asthma by altering the pulmonary immune responses. Using wild-type and transgenic mice expressing the human mannose receptor on smooth muscle cells, we explored the outcome of mannan administration during allergen exposure on the pathogenesis of fungal asthma through measurement of cardinal features of disease such as inflammation, goblet cell number, and airway hyperresponsiveness. Mannan treatment did not alter most hallmarks of allergic airways disease in wild-type mice. Transgenic mice treated with mannan during allergen exposure had an equivalent response to non-mannan-treated allergic mice except for a prominent granulocytic influx into airways and cytokine availability. Our studies suggest no role for mannan as an inflammatory regulator during fungal allergy.
Publisher: Cold Spring Harbor Laboratory
Date: 15-02-2019
DOI: 10.1101/550459
Abstract: Asthma is a chronic airways disease that can be exacerbated during respiratory infections. Our previous findings that the inflammatory state of allergic airways at the time of influenza A virus (IAV) infection in combination with epidemiologic findings that asthmatics were less likely to suffer from severe influenza during the 2009 pandemic suggest that additional complications of influenza, such as increased susceptibility to bacterial superinfection, may be mitigated in the allergic host. To test this hypothesis, we developed a murine model of ‘triple-disease’ in which mice were first rendered allergic to Aspergillus fumigatus and co-infected with IAV and Streptococcus pneumoniae seven days apart. Significant alterations to known synergistic effects of co-infection were noted in the allergic mice including reduced morbidity and mortality, bacterial burden, maintenance of alveolar macrophages, and reduced lung inflammation and damage. The lung microbiome of allergic mice differed from that of non-allergic mice during co-infection. To investigate the impact of the microbiome on the pathogenesis of lung disease, we induced a perturbation with a short course of fluoroquinolone antibiotic that is often prescribed for lung infections. A significant change in the microbiome was complemented with alterations to the inflammatory profile and a drastic increase in pro-inflammatory cytokines in allergic mice which were now susceptible to severe disease from IAV and S. pneumoniae co-infection. Our data suggest that responses to co-infection in allergic hosts likely depends on the immune and microbiome states and that antibiotics should be used with caution in in iduals with underlying chronic lung disease. Author Summary Asthma is a condition of the lungs that affects millions worldwide. Traditionally, respiratory infections are considered to have a negative impact on asthmatics. However, epidemiological data surrounding the 2009 influenza pandemic suggest that asthmatics may be better equipped to counter severe influenza including bacterial pneumonia. Herein, we introduce a novel mouse model system designed to recapitulate an influenza virus and Streptococcal co-infection in a host with fungal asthma. We found that underlying allergic asthma protects against severe disease induced by co-infection. Mice with underlying allergic inflammation had reduced damage to the lungs and did not show signs of respiratory distress. Among the differences noted in the allergic mice that were protected from viral and bacterial co-infection, was the lung microbiome. Allergic mice lost their protection from co-infection after we perturbed their lung microbiome with antibiotics suggesting that the lung microbiome plays a role in host immunity against invading pathogens.
Publisher: The American Association of Immunologists
Date: 15-04-2017
Abstract: Eosinophils are multifunctional cells of the innate immune system linked to allergic inflammation. Asthmatics were more likely to be hospitalized but less likely to suffer severe morbidity and mortality during the 2009 influenza pandemic. These epidemiologic findings were recapitulated in a mouse model of fungal asthma wherein infection during heightened allergic inflammation was protective against influenza A virus (IAV) infection and disease. Our goal was to delineate a mechanism(s) by which allergic asthma may alleviate influenza disease outcome, focused on the hypothesis that pulmonary eosinophilia linked with allergic respiratory disease is able to promote antiviral host defenses against the influenza virus. The transfer of eosinophils from the lungs of allergen-sensitized and challenged mice into influenza virus–infected mice resulted in reduced morbidity and viral burden, improved lung compliance, and increased CD8+ T cell numbers in the airways. In vitro assays with primary or bone marrow–derived eosinophils were used to determine eosinophil responses to the virus using the laboratory strain (A/PR/08/1934) or the pandemic strain (A/CA/04/2009) of IAV. Eosinophils were susceptible to IAV infection and responded by activation, piecemeal degranulation, and upregulation of Ag presentation markers. Virus- or viral peptide–exposed eosinophils induced CD8+ T cell proliferation, activation, and effector functions. Our data suggest that eosinophils promote host cellular immunity to reduce influenza virus replication in lungs, thereby providing a novel mechanism by which hosts with allergic asthma may be protected from influenza morbidity.
Location: United States of America
Location: United States of America
Location: United States of America
No related grants have been discovered for Amali Samarasinghe.