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...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | http://europepmc.org/articles/PMC3744437?pdf=render |
| _version_ | 1828913365112586240 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-13T19:35:51Z |
| format | Article |
| id | doaj.art-f2da2d27d5224298a987a5f1fc4c32c3 |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-12-13T19:35:51Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-f2da2d27d5224298a987a5f1fc4c32c32022-12-21T23:33:49ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352013-01-0178e232910.1371/journal.pntd.0002329The 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 IbrahimJeffrey L BarnesGregory M AnsteadFabio JimenezBruno L TraviAlex G PenicheE Yaneth OsorioSeema S AhujaPeter C MelbyIn 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.http://europepmc.org/articles/PMC3744437?pdf=render |
| spellingShingle | 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. PLoS Neglected Tropical Diseases |
| 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_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_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_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 |
| url | http://europepmc.org/articles/PMC3744437?pdf=render |
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