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Deficiency of lymph node resident dendritic cells and dysregulation of DC chemoattractants in a malnourished mouse model of Leishmania donovani infection.

Authors: Ibrahim, MK  Barnes, JL  Osorio, EY  Anstead, GM  Jimenez, F  Osterholzer, JJ  Travi, BL  Ahuja, SS  Clinton White A, JR  Melby, PC 
Citation: Ibrahim MK, etal., Infect Immun. 2014 May 12.
Pubmed: (View Article at PubMed) PMID:24818662
DOI: Full-text: DOI:10.1128/IAI.01778-14

Malnutrition is thought to contribute to more than one-third of all childhood deaths via increased susceptibility to infection. Malnutrition is a significant risk factor for the development of visceral leishmaniasis, which results from skin inoculation of the intracellular protozoan Leishmania donovani. We previously established a murine model of childhood malnutrition and found that malnutrition decreased lymph node barrier function and increased early dissemination of L. donovani. In this present study, we found reduced numbers of resident dendritic cells (conventional and monocyte-derived), but not migratory dermal dendritic cells, in the skin-draining lymph nodes of L. donovani-infected malnourished mice. Expression of chemokines and their receptors involved in trafficking of dendritic cells and their progenitors to the lymph nodes was dysregulated. C-C chemokine receptor type 2 (CCR2) and its ligands (CCL2 and CCL7) were reduced in lymph nodes of malnourished infected mice, as were CCR2-bearing monocytes/macrophages and monocyte-derived dendritic cells. However, CCR7 and its ligands (CCL19 and CCL21) were increased in the lymph node, and CCR7 was increased on lymph node macrophages and dendritic cells. CCR2-deficient mice recapitulated the profound reduction in the number of resident (but not migratory dermal) dendritic cells in the lymph node, but showed no alteration in the expression of CCL19 and CCL21. Collectively, these results suggest that the malnutrition-related reduction in the lymph node barrier to dissemination of L. donovani is related to insufficient numbers of lymph node resident, but not migratory dermal, dendritic cells. This is likely driven by altered activity of the CCR2 and CCR7 chemoattractant pathways.

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CRRD Object Information
CRRD ID: 8661728
Created: 2014-06-13
Species: All species
Last Modified: 2014-06-13
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.