The malnutrition-related increase in early visceralization of Leishmania donovani is associated with a reduced number of lymph node phagocytes and altered conduit system flow.
In a murine model of moderate childhood malnutrition we found that polynutrient deficiency led to a 4-5-fold increase in early visceralization of L. donovani (3 days post-infection) following cutaneous infection and a 16-fold decrease in lymph node barrier function (p<0.04 for all). To begin to u...
Published in: | PLoS Neglected Tropical Diseases |
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2013
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Online Access: | https://doi.org/10.1371/journal.pntd.0002329 https://doaj.org/article/f2da2d27d5224298a987a5f1fc4c32c3 |
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ftdoajarticles:oai:doaj.org/article:f2da2d27d5224298a987a5f1fc4c32c3 2023-05-15T15:14:19+02:00 The malnutrition-related increase in early visceralization of Leishmania donovani is associated with a reduced number of lymph node phagocytes and altered conduit system flow. Marwa K Ibrahim Jeffrey L Barnes Gregory M Anstead Fabio Jimenez Bruno L Travi Alex G Peniche E Yaneth Osorio Seema S Ahuja Peter C Melby 2013-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002329 https://doaj.org/article/f2da2d27d5224298a987a5f1fc4c32c3 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3744437?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002329 https://doaj.org/article/f2da2d27d5224298a987a5f1fc4c32c3 PLoS Neglected Tropical Diseases, Vol 7, Iss 8, p e2329 (2013) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2013 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002329 2022-12-31T04:27:44Z In a murine model of moderate childhood malnutrition we found that polynutrient deficiency led to a 4-5-fold increase in early visceralization of L. donovani (3 days post-infection) following cutaneous infection and a 16-fold decrease in lymph node barrier function (p<0.04 for all). To begin to understand the mechanistic basis for this malnutrition-related parasite dissemination we analyzed the cellularity, architecture, and function of the skin-draining lymph node. There was no difference in the localization of multiple cell populations in the lymph node of polynutrient deficient (PND) mice, but there was reduced cellularity with fewer CD11c(+)dendritic cells (DCs), fibroblastic reticular cells (FRCs), MOMA-2(+) macrophages, and CD169(+) subcapsular sinus macrophage (p<0.05 for all) compared to the well-nourished (WN) mice. The parasites were equally co-localized with DCs associated with the lymph node conduit network in the WN and PND mice, and were found in the high endothelial venule into which the conduits drain. When a fluorescent low molecular weight (10 kD) dextran was delivered in the skin, there was greater efflux of the marker from the lymph node conduit system to the spleens of PND mice (p<0.04), indicating that flow through the conduit system was altered. There was no evidence of disruption of the conduit or subcapsular sinus architecture, indicating that the movement of parasites into the subcortical conduit region was due to an active process and not from passive movement through a leaking barrier. These results indicate that the impaired capacity of the lymph node to act as a barrier to dissemination of L. donovani infection is associated with a reduced number of lymph node phagocytes, which most likely leads to reduced capture of parasites as they transit through the sinuses and conduit system. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Moma ENVELOPE(143.184,143.184,66.437,66.437) PLoS Neglected Tropical Diseases 7 8 e2329 |
institution |
Open Polar |
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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 Marwa K Ibrahim Jeffrey L Barnes Gregory M Anstead Fabio Jimenez Bruno L Travi Alex G Peniche E Yaneth Osorio Seema S Ahuja Peter C Melby The malnutrition-related increase in early visceralization of Leishmania donovani is associated with a reduced number of lymph node phagocytes and altered conduit system flow. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
In a murine model of moderate childhood malnutrition we found that polynutrient deficiency led to a 4-5-fold increase in early visceralization of L. donovani (3 days post-infection) following cutaneous infection and a 16-fold decrease in lymph node barrier function (p<0.04 for all). To begin to understand the mechanistic basis for this malnutrition-related parasite dissemination we analyzed the cellularity, architecture, and function of the skin-draining lymph node. There was no difference in the localization of multiple cell populations in the lymph node of polynutrient deficient (PND) mice, but there was reduced cellularity with fewer CD11c(+)dendritic cells (DCs), fibroblastic reticular cells (FRCs), MOMA-2(+) macrophages, and CD169(+) subcapsular sinus macrophage (p<0.05 for all) compared to the well-nourished (WN) mice. The parasites were equally co-localized with DCs associated with the lymph node conduit network in the WN and PND mice, and were found in the high endothelial venule into which the conduits drain. When a fluorescent low molecular weight (10 kD) dextran was delivered in the skin, there was greater efflux of the marker from the lymph node conduit system to the spleens of PND mice (p<0.04), indicating that flow through the conduit system was altered. There was no evidence of disruption of the conduit or subcapsular sinus architecture, indicating that the movement of parasites into the subcortical conduit region was due to an active process and not from passive movement through a leaking barrier. These results indicate that the impaired capacity of the lymph node to act as a barrier to dissemination of L. donovani infection is associated with a reduced number of lymph node phagocytes, which most likely leads to reduced capture of parasites as they transit through the sinuses and conduit system. |
format |
Article in Journal/Newspaper |
author |
Marwa K Ibrahim Jeffrey L Barnes Gregory M Anstead Fabio Jimenez Bruno L Travi Alex G Peniche E Yaneth Osorio Seema S Ahuja Peter C Melby |
author_facet |
Marwa K Ibrahim Jeffrey L Barnes Gregory M Anstead Fabio Jimenez Bruno L Travi Alex G Peniche E Yaneth Osorio Seema S Ahuja Peter C Melby |
author_sort |
Marwa K Ibrahim |
title |
The malnutrition-related increase in early visceralization of Leishmania donovani is associated with a reduced number of lymph node phagocytes and altered conduit system flow. |
title_short |
The malnutrition-related increase in early visceralization of Leishmania donovani is associated with a reduced number of lymph node phagocytes and altered conduit system flow. |
title_full |
The malnutrition-related increase in early visceralization of Leishmania donovani is associated with a reduced number of lymph node phagocytes and altered conduit system flow. |
title_fullStr |
The malnutrition-related increase in early visceralization of Leishmania donovani is associated with a reduced number of lymph node phagocytes and altered conduit system flow. |
title_full_unstemmed |
The malnutrition-related increase in early visceralization of Leishmania donovani is associated with a reduced number of lymph node phagocytes and altered conduit system flow. |
title_sort |
malnutrition-related increase in early visceralization of leishmania donovani is associated with a reduced number of lymph node phagocytes and altered conduit system flow. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doi.org/10.1371/journal.pntd.0002329 https://doaj.org/article/f2da2d27d5224298a987a5f1fc4c32c3 |
long_lat |
ENVELOPE(143.184,143.184,66.437,66.437) |
geographic |
Arctic Moma |
geographic_facet |
Arctic Moma |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 7, Iss 8, p e2329 (2013) |
op_relation |
http://europepmc.org/articles/PMC3744437?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002329 https://doaj.org/article/f2da2d27d5224298a987a5f1fc4c32c3 |
op_doi |
https://doi.org/10.1371/journal.pntd.0002329 |
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PLoS Neglected Tropical Diseases |
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8 |
container_start_page |
e2329 |
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