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Resolvin D1 drives establishment of Leishmania amazonensis infection

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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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Effectiveness of Resolvin D1 supplementation in cultures of L. amazonensis- infected human macrophages.Monolayers of infected macrophages were cultured with medium alone or with indicated doses of synthetic RvD1. (A) Intracellular infection burden was assessed by light microscopy; micrographs from L. amazonensis-infected human macrophages unstimulated or treated with RvD1 for 72 h. Original magnification x 1000. (B) Counting of viable parasites was performed as described in Methods. Data represent mean and SE of one representative out two independent experiments. *P < 0.05, **P < 0.01.
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f3: Effectiveness of Resolvin D1 supplementation in cultures of L. amazonensis- infected human macrophages.Monolayers of infected macrophages were cultured with medium alone or with indicated doses of synthetic RvD1. (A) Intracellular infection burden was assessed by light microscopy; micrographs from L. amazonensis-infected human macrophages unstimulated or treated with RvD1 for 72 h. Original magnification x 1000. (B) Counting of viable parasites was performed as described in Methods. Data represent mean and SE of one representative out two independent experiments. *P < 0.05, **P < 0.01.

Mentions: To mimic an environment with high RvD1 levels such as that observed in DCL patients, we supplemented cultures of macrophages infected with L. amazonensis with increasing doses of this lipid mediator. We found an increased infection index as well as augmented number of viable replicating parasites inside macrophages treated with 100 nM RvD1 (Fig. 3A). Photomicrographs illustrated that treatment with RvD1 was able to increase intracellular parasite burden more efficiently than cells in the untreated group (Fig. 3A).


Resolvin D1 drives establishment of Leishmania amazonensis infection
Effectiveness of Resolvin D1 supplementation in cultures of L. amazonensis- infected human macrophages.Monolayers of infected macrophages were cultured with medium alone or with indicated doses of synthetic RvD1. (A) Intracellular infection burden was assessed by light microscopy; micrographs from L. amazonensis-infected human macrophages unstimulated or treated with RvD1 for 72 h. Original magnification x 1000. (B) Counting of viable parasites was performed as described in Methods. Data represent 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

f3: Effectiveness of Resolvin D1 supplementation in cultures of L. amazonensis- infected human macrophages.Monolayers of infected macrophages were cultured with medium alone or with indicated doses of synthetic RvD1. (A) Intracellular infection burden was assessed by light microscopy; micrographs from L. amazonensis-infected human macrophages unstimulated or treated with RvD1 for 72 h. Original magnification x 1000. (B) Counting of viable parasites was performed as described in Methods. Data represent mean and SE of one representative out two independent experiments. *P < 0.05, **P < 0.01.
Mentions: To mimic an environment with high RvD1 levels such as that observed in DCL patients, we supplemented cultures of macrophages infected with L. amazonensis with increasing doses of this lipid mediator. We found an increased infection index as well as augmented number of viable replicating parasites inside macrophages treated with 100 nM RvD1 (Fig. 3A). Photomicrographs illustrated that treatment with RvD1 was able to increase intracellular parasite burden more efficiently than cells in the untreated group (Fig. 3A).

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