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Resolvin D1 drives establishment of Leishmania amazonensis infection

View Article: PubMed Central - PubMed

ABSTRACT

Previous studies have indicated that the balance between different eicosanoids reflect the intensity of the inflammatory profile in patients with tegumentary leishmaniasis. More recently, pro-resolution lipid mediators have been shown to play critical roles in dampening pathological inflammatory processes to reestablish homeostasis in a diverse range of experimental settings. Among these lipid mediator, resolvins from D series have been described as potent anti-inflammatory and immunomodulatory mediators, and its activities include inhibition of leukocyte chemotaxis and blockage production of proinflammatory cytokines, while increasing the expression of regulatory mediators. Whether resolvins play significant roles in establishment and persistence of Leishmania infection is currently unknown. We addressed this question in the current study by assessing circulating levels of D-series resolvins in tegumentary leishmaniasis patients presenting with localized or diffuse disease. We found heightened expression of resolvin D1 in diffuse cutaneous leishmaniasis which was correlated with expression profile of biomarkers associated with disease pathogenesis. Additional in vitro experiments using primary human macrophages indicated that resolvin D1 may promote intracellular Leishmania amazonensis replication through a mechanism associated with induction of heme oxygenase-1. These results suggest that targeting resolvin D1 could serve as potential strategy for host directed therapy in diffuse cutaneous leishmaniasis.

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Related in: MedlinePlus

L. amazonensis infection induces the RvD1 production by macrophages.Monocyte-derived human macrophages (n = 6) were infected with L. amazonensis (MOI 6:1). RvD1 levels were measured in culture supernatants at indicated timepoints post-infection. Data shown are mean and SE of one representative out two independent experiments. *P < 0.05, **P < 0.01.
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f2: L. amazonensis infection induces the RvD1 production by macrophages.Monocyte-derived human macrophages (n = 6) were infected with L. amazonensis (MOI 6:1). RvD1 levels were measured in culture supernatants at indicated timepoints post-infection. Data shown are mean and SE of one representative out two independent experiments. *P < 0.05, **P < 0.01.

Mentions: To better explore the direct association between RvD1 and Leishmania infection, we employed an in vitro system using primary human monocyte-derived macrophages. In cultures of macrophages infected with L. amazonensis, we observed a >1.5-fold induction of RvD1 concentrations in supernatants at 4 h post-infection compared to that in uninfected cell cultures (Fig. 2). This infection-driven induction in RvD1 production was transient as the detected concentrations significantly dropped at as soon as 6 h post infection and persisted for up to 48 h at low levels similar to pre-infection status (Fig. 2).


Resolvin D1 drives establishment of Leishmania amazonensis infection
L. amazonensis infection induces the RvD1 production by macrophages.Monocyte-derived human macrophages (n = 6) were infected with L. amazonensis (MOI 6:1). RvD1 levels were measured in culture supernatants at indicated timepoints post-infection. Data shown are mean and SE of one representative out two independent experiments. *P < 0.05, **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5385529&req=5

f2: L. amazonensis infection induces the RvD1 production by macrophages.Monocyte-derived human macrophages (n = 6) were infected with L. amazonensis (MOI 6:1). RvD1 levels were measured in culture supernatants at indicated timepoints post-infection. Data shown are mean and SE of one representative out two independent experiments. *P < 0.05, **P < 0.01.
Mentions: To better explore the direct association between RvD1 and Leishmania infection, we employed an in vitro system using primary human monocyte-derived macrophages. In cultures of macrophages infected with L. amazonensis, we observed a >1.5-fold induction of RvD1 concentrations in supernatants at 4 h post-infection compared to that in uninfected cell cultures (Fig. 2). This infection-driven induction in RvD1 production was transient as the detected concentrations significantly dropped at as soon as 6 h post infection and persisted for up to 48 h at low levels similar to pre-infection status (Fig. 2).

View Article: PubMed Central - PubMed

ABSTRACT

Previous studies have indicated that the balance between different eicosanoids reflect the intensity of the inflammatory profile in patients with tegumentary leishmaniasis. More recently, pro-resolution lipid mediators have been shown to play critical roles in dampening pathological inflammatory processes to reestablish homeostasis in a diverse range of experimental settings. Among these lipid mediator, resolvins from D series have been described as potent anti-inflammatory and immunomodulatory mediators, and its activities include inhibition of leukocyte chemotaxis and blockage production of proinflammatory cytokines, while increasing the expression of regulatory mediators. Whether resolvins play significant roles in establishment and persistence of Leishmania infection is currently unknown. We addressed this question in the current study by assessing circulating levels of D-series resolvins in tegumentary leishmaniasis patients presenting with localized or diffuse disease. We found heightened expression of resolvin D1 in diffuse cutaneous leishmaniasis which was correlated with expression profile of biomarkers associated with disease pathogenesis. Additional in vitro experiments using primary human macrophages indicated that resolvin D1 may promote intracellular Leishmania amazonensis replication through a mechanism associated with induction of heme oxygenase-1. These results suggest that targeting resolvin D1 could serve as potential strategy for host directed therapy in diffuse cutaneous leishmaniasis.

No MeSH data available.


Related in: MedlinePlus