IL-4 receptor dependent expansion of lung CD169+ macrophages in microfilaria-driven inflammation.
Lung disease is regularly reported in human filarial infections but the molecular pathogenesis of pulmonary filariasis is poorly understood. We used Litomosoides sigmodontis, a rodent filaria residing in the pleural cavity responsible for pleural inflammation, to model responses to human filarial in...
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ftdoajarticles:oai:doaj.org/article:2bfc6f2c66f34b1884638bed65d71050 2023-05-15T15:11:05+02:00 IL-4 receptor dependent expansion of lung CD169+ macrophages in microfilaria-driven inflammation. Frédéric Fercoq Estelle Remion Stefan J Frohberger Nathaly Vallarino-Lhermitte Achim Hoerauf John Le Quesne Frédéric Landmann Marc P Hübner Leo M Carlin Coralie Martin 2019-08-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0007691 https://doaj.org/article/2bfc6f2c66f34b1884638bed65d71050 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0007691 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0007691 https://doaj.org/article/2bfc6f2c66f34b1884638bed65d71050 PLoS Neglected Tropical Diseases, Vol 13, Iss 8, p e0007691 (2019) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2019 ftdoajarticles https://doi.org/10.1371/journal.pntd.0007691 2022-12-31T08:23:42Z Lung disease is regularly reported in human filarial infections but the molecular pathogenesis of pulmonary filariasis is poorly understood. We used Litomosoides sigmodontis, a rodent filaria residing in the pleural cavity responsible for pleural inflammation, to model responses to human filarial infections and probe the mechanisms. Wild-type and Th2-deficient mice (ΔdblGata1 and Il-4receptor(r)a-/-/IL-5-/-) were infected with L. sigmodontis. Survival and growth of adult filariae and prevalence and density of microfilariae were evaluated. Cells and cytokines in the pleural cavity and bronchoalveolar space were characterized by imaging, flow cytometry and ELISA. Inflammatory pathways were evaluated by transcriptomic microarrays and lungs were isolated and analyzed for histopathological signatures. 40% of WT mice were amicrofilaremic whereas almost all mutant mice display blood microfilaremia. Microfilariae induced pleural, bronchoalveolar and lung-tissue inflammation associated with an increase in bronchoalveolar eosinophils and perivascular macrophages, production of mucus, visceral pleura alterations and fibrosis. Inflammation and pathology were decreased in Th2-deficient mice. An IL-4R-dependent increase of CD169 was observed on pleural and bronchoalveolar macrophages in microfilaremic mice. CD169+ tissue-resident macrophages were identified in the lungs with specific localizations. Strikingly, CD169+ macrophages increased significantly in the perivascular area in microfilaremic mice. These data describe lung inflammation and pathology in chronic filariasis and emphasize the role of Th2 responses according to the presence of microfilariae. It is also the first report implicating CD169+ lung macrophages in response to a Nematode infection. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 13 8 e0007691 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Frédéric Fercoq Estelle Remion Stefan J Frohberger Nathaly Vallarino-Lhermitte Achim Hoerauf John Le Quesne Frédéric Landmann Marc P Hübner Leo M Carlin Coralie Martin IL-4 receptor dependent expansion of lung CD169+ macrophages in microfilaria-driven inflammation. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Lung disease is regularly reported in human filarial infections but the molecular pathogenesis of pulmonary filariasis is poorly understood. We used Litomosoides sigmodontis, a rodent filaria residing in the pleural cavity responsible for pleural inflammation, to model responses to human filarial infections and probe the mechanisms. Wild-type and Th2-deficient mice (ΔdblGata1 and Il-4receptor(r)a-/-/IL-5-/-) were infected with L. sigmodontis. Survival and growth of adult filariae and prevalence and density of microfilariae were evaluated. Cells and cytokines in the pleural cavity and bronchoalveolar space were characterized by imaging, flow cytometry and ELISA. Inflammatory pathways were evaluated by transcriptomic microarrays and lungs were isolated and analyzed for histopathological signatures. 40% of WT mice were amicrofilaremic whereas almost all mutant mice display blood microfilaremia. Microfilariae induced pleural, bronchoalveolar and lung-tissue inflammation associated with an increase in bronchoalveolar eosinophils and perivascular macrophages, production of mucus, visceral pleura alterations and fibrosis. Inflammation and pathology were decreased in Th2-deficient mice. An IL-4R-dependent increase of CD169 was observed on pleural and bronchoalveolar macrophages in microfilaremic mice. CD169+ tissue-resident macrophages were identified in the lungs with specific localizations. Strikingly, CD169+ macrophages increased significantly in the perivascular area in microfilaremic mice. These data describe lung inflammation and pathology in chronic filariasis and emphasize the role of Th2 responses according to the presence of microfilariae. It is also the first report implicating CD169+ lung macrophages in response to a Nematode infection. |
format |
Article in Journal/Newspaper |
author |
Frédéric Fercoq Estelle Remion Stefan J Frohberger Nathaly Vallarino-Lhermitte Achim Hoerauf John Le Quesne Frédéric Landmann Marc P Hübner Leo M Carlin Coralie Martin |
author_facet |
Frédéric Fercoq Estelle Remion Stefan J Frohberger Nathaly Vallarino-Lhermitte Achim Hoerauf John Le Quesne Frédéric Landmann Marc P Hübner Leo M Carlin Coralie Martin |
author_sort |
Frédéric Fercoq |
title |
IL-4 receptor dependent expansion of lung CD169+ macrophages in microfilaria-driven inflammation. |
title_short |
IL-4 receptor dependent expansion of lung CD169+ macrophages in microfilaria-driven inflammation. |
title_full |
IL-4 receptor dependent expansion of lung CD169+ macrophages in microfilaria-driven inflammation. |
title_fullStr |
IL-4 receptor dependent expansion of lung CD169+ macrophages in microfilaria-driven inflammation. |
title_full_unstemmed |
IL-4 receptor dependent expansion of lung CD169+ macrophages in microfilaria-driven inflammation. |
title_sort |
il-4 receptor dependent expansion of lung cd169+ macrophages in microfilaria-driven inflammation. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2019 |
url |
https://doi.org/10.1371/journal.pntd.0007691 https://doaj.org/article/2bfc6f2c66f34b1884638bed65d71050 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 13, Iss 8, p e0007691 (2019) |
op_relation |
https://doi.org/10.1371/journal.pntd.0007691 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0007691 https://doaj.org/article/2bfc6f2c66f34b1884638bed65d71050 |
op_doi |
https://doi.org/10.1371/journal.pntd.0007691 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
13 |
container_issue |
8 |
container_start_page |
e0007691 |
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1766341996752928768 |