| 1. |
- Brownlie, Rebecca J, et al.
(författare)
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Distinct cell-specific control of autoimmunity and infection by FcgammaRIIb.
- 2008
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 205:4, s. 883-95
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Tidskriftsartikel (refereegranskat)abstract
- FcgammaRIIb is an inhibitory Fc receptor expressed on B cells and myeloid cells. It is important in controlling responses to infection, and reduced expression or function predisposes to autoimmunity. To determine if increased expression of FcgammaRIIb can modulate these processes, we created transgenic mice overexpressing FcgammaRIIb on B cells or macrophages. Overexpression of FcgammaRIIb on B cells reduced the immunoglobulin G component of T-dependent immune responses, led to early resolution of collagen-induced arthritis (CIA), and reduced spontaneous systemic lupus erythematosus (SLE). In contrast, overexpression on macrophages had no effect on immune responses, CIA, or SLE but increased mortality after Streptococcus pneumoniae infection. These results help define the role of FcgammaRIIb in immune responses, demonstrate the contrasting roles played by FcgammaRIIb on B cells and macrophages in the control of infection and autoimmunity, and emphasize the therapeutic potential for modulation of FcgammaRIIb expression on B cells in inflammatory and autoimmune disease.
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| 2. |
- Hepburn, Lucy, et al.
(författare)
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A Spaetzle-like role for nerve growth factor beta in vertebrate immunity to Staphylococcus aureus
- 2014
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6209, s. 641-646
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Tidskriftsartikel (refereegranskat)abstract
- Many key components of innate immunity to infection are shared between Drosophila and humans. However, the fly Toll ligand Spaetzle is not thought to have a vertebrate equivalent. We have found that the structurally related cystine-knot protein, nerve growth factor β (NGFβ), plays an unexpected Spaetzle-like role in immunity to Staphylococcus aureus infection in chordates. Deleterious mutations of either human NGFβ or its high-affinity receptor tropomyosin-related kinase receptor A (TRKA) were associated with severe S. aureus infections. NGFβ was released by macrophages in response to S. aureus exoproteins through activation of the NOD-like receptors NLRP3 and NLRP4 and enhanced phagocytosis and superoxide-dependent killing, stimulated proinflammatory cytokine production, and promoted calcium-dependent neutrophil recruitment. TrkA knockdown in zebrafish increased susceptibility to S. aureus infection, confirming an evolutionarily conserved role for NGFβ-TRKA signaling in pathogen-specific host immunity.
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| 3. |
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| 4. |
- Martineau, Adrian R., et al.
(författare)
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IFN-gamma- and TNF-independent vitamin D-inducible human suppression of mycobacteria: The role of cathelicidin LL-37
- 2007
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Ingår i: Journal of Immunology. - 1550-6606. ; 178:11, s. 7190-7198
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin D deficiency is associated with susceptibility to tuberculosis, and its biologically active metabolite, 1 alpha,25 dihydroxyvitamin D-3 (1 alpha,25(OH)(2)D-3), has pleiotropic immune effects. The mechanisms by which 1 alpha,25(OH)(2)D-3 protects against tuberculosis are incompletely understood. 1 alpha,25(OH)(2)D-3 reduced the growth of mycobacteria in infected human PBMC cultures in a dose-dependent fashion. Coculture with agonists or antagonists of the membrane or nuclear vitamin D receptors indicated that these effects were primarily mediated by the nuclear vitamin D receptors. 1 alpha,25(OH)(2)D-3 reduced transcription and secretion of protective IFN-gamma, IL-12p40, and TNF in infected PBMC and macrophages, indicating that 1 alpha,25(OH)(2)D-3 does not mediate protection via these cytokines. Although NOM was up-regulated by 1 alpha,25(OH)(2)D-3, inhibition of NO formation marginally affected the suppressive effect of 1 alpha,25(OH)(2)D-3 on bacillus Calmette Guerin in infected cells. By contrast, 1 alpha,25(OH)(2)D-3 strongly up-regulated the cathelicidin hCAP-18 gene, and some hCAP-18 polypeptide colocalized with CD14 in 1 alpha,25(OH)(2)D-3 stimulated PBMC, although no detectable LL-37 peptide was found in supernatants from similar 1 alpha,25(OH)(2)D-3-stimulated PBMC cultures. A total of 200 mu g/ml of the active peptide LL-37, in turn, reduced the growth of Mycobacterium tuberculosis in culture by 75.7%. These findings suggest that vitamin D contributes to protection against TB by '' nonclassical '' mechanisms that include the induction of antimicrobial peptides.
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| 5. |
- Morawska, Lidia, et al.
(författare)
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COVID-19 and airborne transmission : science rejected, lives lost : can society do better?
- 2023
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Ingår i: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - : Oxford University Press (OUP). - 1537-6591. ; 76:10, s. 1854-1859
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Tidskriftsartikel (refereegranskat)abstract
- This is an account that should be heard of an important struggle: the struggle of a large group of experts who came together at the beginning of the Covid-19 pandemic to warn the world about the risk of airborne transmission and the consequences of ignoring it. We alerted the World Health Organization (WHO) about the potential significance of the airborne transmission of SARS-CoV-2 and the urgent need to control it, but our concerns were dismissed. Here we describe how this happened and the consequences. We hope that by reporting this story, we can raise awareness of the importance of interdisciplinary collaboration and the need to be open to new evidence, and to prevent it from happening again. Acknowledgement of an issue and the emergence of new evidence related to it, is the first necessary step towards finding effective mitigation solutions.
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| 6. |
- Morawska, Lidia, et al.
(författare)
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How can airborne transmission of COVID-19 indoors be minimised?
- 2020
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Ingår i: Environment International. - : Elsevier BV. - 1873-6750 .- 0160-4120. ; 142
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Tidskriftsartikel (refereegranskat)abstract
- During the rapid rise in COVID-19 illnesses and deaths globally, and notwithstanding recommended precautions, questions are voiced about routes of transmission for this pandemic disease. Inhaling small airborne droplets is probable as a third route of infection, in addition to more widely recognized transmission via larger respiratory droplets and direct contact with infected people or contaminated surfaces. While uncertainties remain regarding the relative contributions of the different transmission pathways, we argue that existing evidence is sufficiently strong to warrant engineering controls targeting airborne transmission as part of an overall strategy to limit infection risk indoors. Appropriate building engineering controls include sufficient and effective ventilation, possibly enhanced by particle filtration and air disinfection, avoiding air recirculation and avoiding overcrowding. Often, such measures can be easily implemented and without much cost, but if only they are recognised as significant in contributing to infection control goals. We believe that the use of engineering controls in public buildings, including hospitals, shops, offices, schools, kindergartens, libraries, restaurants, cruise ships, elevators, conference rooms or public transport, in parallel with effective application of other controls (including isolation and quarantine, social distancing and hand hygiene), would be an additional important measure globally to reduce the likelihood of transmission and thereby protect healthcare workers, patients and the general public.
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| 7. |
- Morawska, Lidia, et al.
(författare)
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Mandating indoor air quality for public buildings : if some countries lead by example, standards may increasingly become normalized
- 2024
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Ingår i: Science. - 0036-8075. ; 383:6690, s. 1418-1420
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Tidskriftsartikel (refereegranskat)abstract
- People living in urban and industrialized societies, which are expanding globally, spend more than 90% of their time in the indoor environment, breathing indoor air (IA). Despite decades of research and advocacy, most countries do not have legislated indoor air quality (IAQ) performance standards for public spaces that address concentration levels of IA pollutants. Few building codes address operation, maintenance, and retrofitting, and most do not focus on airborne disease transmission. But the COVID-19 pandemic has made all levels of society, from community members to decision-makers, realize the importance of IAQ for human health, wellbeing, productivity, and learning. We propose that IAQ standards be mandatory for public spaces. Although enforcement of IAQ performance standards in homes is not possible, homes must be designed and equipped so that they could meet the standards.For the past two decades, scientists have called for national IAQ standards and laws to be established (2), but so far, little action has been taken. The approach to IA contrasts sharply with outdoor air, for which quality is regulated and monitored and compliance with regulations is enforced. The World Health Organization (WHO) Global Air Quality Guidelines (AQG) published in 2021 provide recommendations for concentration levels of six pollutants and their averaging times (PM2.5, PM10, NO2, SO2, CO, and O3) and apply to both outdoor air and IA (3).In cases for which IAQ standard and guideline values were established by national or association working groups, the outcomes were inconsistent; often the criteria for the same parameter differed by orders of magnitude. The reasons cited for limited progress include different criteria in the selection of the critical study, in the starting point, and in the derivation procedure; the complex political, social, and legislative situation regarding IAQ; the lack of an open, systematic, and harmonized approach; and that establishing an IAQ standard is always the result of a compromise between scientific knowledge and political will. Because of the heterogenous landscape of approaches needed, such barriers remain intact despite the considerable IAQ research and evidence base developed over the past decades.
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