Abstract
BackgroundIn vitro studies show that Leishmania infection decreases the adhesion of inflammatory phagocytes to connective tissue by a mechanism dependent on the modulation of integrin function. However, we know little about the influence of this reduction in leukocyte adhesion on parasite dissemination from the infection site.MethodsIn this work, we used a model of chronic peritonitis induced by thioglycollate to study the effect of L. amazonensis infection on the ability of inflammatory phagocyte populations to migrate from an inflammatory site to the draining lymph node. Uninfected or Leishmania-infected thioglycollate-elicited peritoneal exudate cells were transferred from C57BL/6 to BALB/c mice or from Ly5.1+ to Ly5.1- mice. The transferred cells were injected into the peritoneal cavity and tracked to the draining lymph node.ResultsMigrating cells corresponded to approximately 1% of the injected leukocytes. The proportion of migrating CD11b+CD11c+ (myeloid dendritic cell) was lower after incubation with Leishmania (1.3 to 2.6 times lower in the experiments using C57BL/6 to BALB/c animals and 2.7 to 3.4 times lower in the experiments using Ly5.1+ to Ly5.1- animals) than after leukocyte incubation with medium alone (P < 0.01). There was no consistent decrease in the migration of CD11b+F4/80+ (macrophage) or SSChi GR-1+ (neutrophil) populations.ConclusionsCoincubation with Leishmania changes the migratory pattern of dendritic cells in vivo. Such changes in dendritic cell migration may be associated with immunological events that maintain inflammation at the sites of infection.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-450) contains supplementary material, which is available to authorized users.
Highlights
In vitro studies show that Leishmania infection decreases the adhesion of inflammatory phagocytes to connective tissue by a mechanism dependent on the modulation of integrin function
We showed that coincubation with Leishmania impairs the adhesion of different mononuclear phagocytes to inflamed connective tissues and to connective matrix components in vitro and that this decrease in cell adherence correlates with the proportion of infected phagocytes and the parasite burden in the cell [11,12]
[11,20,21]; (2) these cells are present in large numbers, allowing easy collection, in vitro manipulation and reinjection; (3) the adherence of the peritoneal exudate cells (PEC) to the connective tissue is decreased after cultivation with Leishmania [11,12]; and (4) the emigration of mononuclear phagocytes from the peritoneal cavity to the lymph nodes observed in this in vivo migration system is dependent on Very Late Antigen-4 (VLA-4) [22], a molecule that we have shown to have altered function in Leishmania-infected phagocytes [8]
Summary
In vitro studies show that Leishmania infection decreases the adhesion of inflammatory phagocytes to connective tissue by a mechanism dependent on the modulation of integrin function. At the Leishmania inoculation site, various phagocytes have the potential to phagocytize and transport live amastigotes or killed parasites, which in the interior of the mononuclear phagocytes in the skin lesion and in the marginal sinus of the draining lymph nodes, suggesting that these phagocytes continuously transport parasite and parasite molecules [4]. Amastigotes are maintained in the interior of the mononuclear phagocytes, and the immunoreactions elicited by these cells are associated with different types of nodular lesions or ulcers. We still know very little about the mechanisms controlling the ability of these cells containing live parasite or parasite fragments to remain in the infection site or to migrate to the draining lymph node. We showed that coincubation with Leishmania impairs the adhesion of different mononuclear phagocytes to inflamed connective tissues and to connective matrix components in vitro and that this decrease in cell adherence correlates with the proportion of infected phagocytes and the parasite burden in the cell [11,12]
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