ORCID Profile
0000-0001-8733-2945
Current Organisation
University of Oxford
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Publisher: Wiley
Date: 10-03-2022
DOI: 10.1111/IMCB.12536
Abstract: Recent advances in the field of host immunity against parasitic nematodes have revealed the importance of macrophages in trapping tissue migratory larvae. Protective immune mechanisms against the rodent hookworm Nippostrongylus brasiliensis (Nb) are mediated, at least in part, by IL‐4‐activated macrophages that bind and trap larvae in the lung. However, it is still not clear how host macrophages recognize the parasite. An in vitro co‐culture system of bone marrow‐derived macrophages and Nb infective larvae was utilized to screen for the possible ligand–receptor pair involved in macrophage attack of larvae. Competitive binding assays revealed an important role for β‐glucan recognition in the process. We further identified a role for CD11b and the non‐classical pattern recognition receptor ephrin‐A2 (EphA2), but not the highly expressed β‐glucan dectin‐1 receptor, in this process of recognition. This work raises the possibility that parasitic nematodes synthesize β‐glucans and it identifies CD11b and ephrin‐A2 as important pattern recognition receptors involved in the host recognition of these evolutionary old pathogens. To our knowledge, this is the first time that EphA2 has been implicated in immune responses to a helminth.
Publisher: European Respiratory Society
Date: 28-09-2019
Publisher: JoLS, Journal of Life Sciences
Date: 03-2020
Publisher: Springer Science and Business Media LLC
Date: 09-09-2019
DOI: 10.1038/S41590-019-0451-9
Abstract: The revolution in microbiota research over the past decade has provided invaluable knowledge about the function of the microbial species that inhabit the human body. It has become widely accepted that these microorganisms, collectively called 'the microbiota', engage in networks of interactions with each other and with the host that aim to benefit both the microbial members and the mammalian members of this unique ecosystem. The lungs, previously thought to be sterile, are now known to harbor a unique microbiota and, additionally, to be influenced by microbial signals from distal body sites, such as the intestine. Here we review the role of the lung and gut microbiotas in respiratory health and disease and highlight the main pathways of communication that underlie the gut-lung axis.
Publisher: Frontiers Media SA
Date: 30-08-2021
Abstract: Bronchopulmonary dysplasia (BPD) is a severe lung disease that affects preterm infants receiving oxygen therapy. No standardized, clinically-relevant BPD model exists, h ering efforts to understand and treat this disease. This study aimed to evaluate and confirm a candidate model of acute and chronic BPD, based on exposure of neonatal mice to a high oxygen environment during key lung developmental stages affected in preterm infants with BPD. Neonatal C57BL/6 mouse pups were exposed to 75% oxygen from postnatal day (PN)-1 for 5, 8, or 14 days, and their lungs were examined at PN14 and PN40. While all mice showed some degree of lung damage, mice exposed to hyperoxia for 8 or 14 days exhibited the greatest septal wall thickening and airspace enlargement. Furthermore, when assessed at PN40, mice exposed for 8 or 14 days to supplemental oxygen exhibited augmented septal wall thickness and emphysema, with the severity increased with the longer exposure, which translated into a decline in respiratory function at PN80 in the 14-day model. In addition to this, mice exposed to hyperoxia for 8 days showed significant expansion of alveolar epithelial type II cells as well as the greatest fibrosis when assessed at PN40 suggesting a healing response, which was not seen in mice exposed to high oxygen for a longer period. While evidence of lung inflammation was apparent at PN14, chronic inflammation was absent from all three models. Finally, exposure to high oxygen for 14 days also induced concurrent outer retinal degeneration. This study shows that early postnatal exposure to high oxygen generates hallmark acute and chronic pathologies in mice that highlights its use as a translational model of BPD.
Publisher: Elsevier BV
Date: 09-2020
Publisher: American Association for the Advancement of Science (AAAS)
Date: 05-11-2021
Abstract: Small proline-rich protein 2A regulates the intestinal microbiota
Publisher: Wiley
Date: 2021
DOI: 10.1002/CTI2.1322
Abstract: Bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) are two neonatal diseases of major clinical importance, arising in large part as a consequence of supplemental oxygen therapy used to promote the survival of preterm infants. The presence of coincident inflammation in the lungs and eyes of neonates receiving oxygen therapy indicates that a dysregulated immune response serves as a potential common pathogenic factor for both diseases. This review examines the current state of knowledge of immunological dysregulation in BPD and ROP, identifying similarities in the cellular subsets and inflammatory cytokines that are found in the alveoli and retina during the active phase of these diseases, indicating possible mechanistic overlap. In addition, we highlight gaps in the understanding of whether these responses emerge independently in the lung and retina as a consequence of oxygen exposure or arise because of inflammatory spill‐over from the lung. As BPD and ROP are anatomically distinct, they are often considered discreet disease entities and are therefore treated separately. We propose that an improved understanding of the relationship between BPD and ROP is key to the identification of novel therapeutic targets to treat or prevent both conditions simultaneously.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Lakshanie C Wickramasinghe.