| 1. |
- Andersson, Cecilia K, et al.
(author)
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Distal respiratory tract viral infections in young children trigger a marked increase in alveolar mast cells
- 2018
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In: ERJ Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 4:4
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Journal article (peer-reviewed)abstract
- Viral infections predispose to the development of childhood asthma, a disease associated with increased lung mast cells (MCs). This study investigated whether viral lower respiratory tract infections (LRTIs) can already evoke a MC response during childhood. Lung tissue from young children who died following LRTIs were processed for immunohistochemical identification of MCs. Children who died from nonrespiratory causes served as controls. MCs were examined in relation to sensitisation in infant mice exposed to allergen during influenza A infection. Increased numbers of MCs were observed in the alveolar parenchyma of children infected with LRTIs (median (range) 12.5 (0-78) MCs per mm2) compared to controls (0.63 (0-4) MCs per mm2, p=0.0005). The alveolar MC expansion was associated with a higher proportion of CD34+ tryptase+ progenitors (controls: 0% (0-1%); LRTIs: 0.9% (0-3%) CD34+ MCs (p=0.01)) and an increased expression of the vascular cell adhesion molecule (VCAM)-1 (controls: 0.2 (0.07-0.3); LRTIs: 0.3 (0.02-2) VCAM-1 per mm2 (p=0.04)). Similarly, infant mice infected with H1N1 alone or together with house dust mite (HDM) developed an increase in alveolar MCs (saline: 0.4 (0.3-0.5); HDM: 0.6 (0.4-0.9); H1N1: 1.4 (0.4-2.0); HDM+H1N1: 2.2 (1.2-4.4) MCs per mm2 (p<0.0001)). Alveolar MCs continued to increase and remained significantly higher into adulthood when exposed to H1N1+HDM (day 36: 2.2 (1.2-4.4); day 57: 4.6 (1.6-15) MCs per mm2 (p=0.01)) but not when infected with H1N1 alone. Our data demonstrate that distal viral infections in young children evoke a rapid accumulation of alveolar MCs. Apart from revealing a novel immune response to distal infections, our data may have important implications for the link between viral infections during early childhood and subsequent asthma development.
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| 2. |
- Chu, Derek K, et al.
(author)
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Indigenous enteric eosinophils control DCs to initiate a primary Th2 immune response in vivo.
- 2014
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In: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 211:8, s. 1657-1672
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Journal article (peer-reviewed)abstract
- Eosinophils natively inhabit the small intestine, but a functional role for them there has remained elusive. Here, we show that eosinophil-deficient mice were protected from induction of Th2-mediated peanut food allergy and anaphylaxis, and Th2 priming was restored by reconstitution with il4(+/+) or il4(-/-) eosinophils. Eosinophils controlled CD103(+) dendritic cell (DC) activation and migration from the intestine to draining lymph nodes, events necessary for Th2 priming. Eosinophil activation in vitro and in vivo led to degranulation of eosinophil peroxidase, a granule protein whose enzymatic activity promoted DC activation in mice and humans in vitro, and intestinal and extraintestinal mouse DC activation and mobilization to lymph nodes in vivo. Further, eosinophil peroxidase enhanced responses to ovalbumin seen after immunization. Thus, eosinophils can be critical contributors to the intestinal immune system, and granule-mediated shaping of DC responses can promote both intestinal and extraintestinal adaptive immunity.
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| 3. |
- Jiménez-Saiz, Rodrigo, et al.
(author)
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Microbial Regulation of Enteric Eosinophils and Its Impact on Tissue Remodeling and Th2 Immunity
- 2020
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In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 11
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Journal article (peer-reviewed)abstract
- Eosinophils have emerged as multifaceted cells that contribute to tissue homeostasis. However, the impact of the microbiota on their frequency and function at mucosal sites remains unclear. Here, we investigated the role of the microbiota in the regulation of enteric eosinophils. We found that small intestinal (SI) eosinophilia was significantly greater in germ-free (GF) mice compared to specific pathogen free (SPF) controls. This was associated with changes in the production of enteric signals that regulate eosinophil attraction and survival, and was fully reversed by complex colonization. Additionally, SI eosinophils of GF mice exhibited more cytoplasmic protrusions and less granule content than SPF controls. Lastly, we generated a novel strain of eosinophil-deficient GF mice. These mice displayed intestinal fibrosis and were less prone to allergic sensitization as compared to GF controls. Overall, our study demonstrates that commensal microbes regulate intestinal eosinophil frequency and function, which impacts tissue repair and allergic sensitization to food antigens. These data support a critical interplay between the commensal microbiota and intestinal eosinophils in shaping homeostatic, innate, and adaptive immune processes in health and disease.
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| 4. |
- Rydell-Törmänen, Kristina, et al.
(author)
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Induction of Vascular Remodeling in the Lung by Chronic House Dust Mite Exposure.
- 2008
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In: American Journal of Respiratory Cell and Molecular Biology. - 1535-4989. ; 39, s. 61-67
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Journal article (peer-reviewed)abstract
- Structural changes to the lung are known to be associated with chronic asthma. In addition to the well-described alterations to the airway wall, asthma is also associated with vascular modifications, although this aspect of remodeling is poorly understood. We therefore sought to evaluate the character and kinetics of vascular remodeling in response to chronic aeroallergen exposure. However, since many OVA-driven models used to investigate allergic airway disease do so in the absence of persistent airway inflammation, we chose instead to employ a protocol of chronic respiratory exposure to house dust mite extract (HDM), which has been shown to induce persistent airway inflammation consistent with that seen in human asthmatics. Mice were exposed to HDM intranasally for 7 or 20 consecutive weeks, and resolution of the inflammatory and remodeling response to allergen was investigated 4 weeks following the end of a 7-week exposure protocol. Measures of vascular remodeling, including total collagen deposition, procollagen I-production, endothelial and smooth muscle cell proliferation, smooth muscle area and presence of myofibroblasts were investigated histologically in lung vessels of different sizes and locations. We observed an increase in total collagen content which did not resolve upon cessation of allergen exposure. Other parameters were significantly increased following 7 and/or 20 weeks of allergen exposure, but returned to baseline following allergen withdrawal. We conclude that respiratory HDM exposure induces not only airway remodeling, but also pulmonary vascular remodeling, and in accordance with airway remodeling, some components of these structural changes may be irreversible.
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