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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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RvD1 induces the HO-1 production in L. amazonensis-infected human macrophages.Supernatants from infected macrophages were collected after 24 h post infection and evaluated for the levels of transforming growth factor β (TGF-β; A) whereas hemoxygenase-1 (HO-1; B) protein expression was assessed in cell extracts as described in Methods. Data shown are mean and SE of one representative out two independent experiments. *P < 0.05, **P < 0.01.
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f5: RvD1 induces the HO-1 production in L. amazonensis-infected human macrophages.Supernatants from infected macrophages were collected after 24 h post infection and evaluated for the levels of transforming growth factor β (TGF-β; A) whereas hemoxygenase-1 (HO-1; B) protein expression was assessed in cell extracts as described in Methods. Data shown are mean and SE of one representative out two independent experiments. *P < 0.05, **P < 0.01.

Mentions: It is well established that induction of cytokines is a critical evasion mechanism used by Leishmania parasites1013. Here, we confirmed that L. amazonensis infection induces TGF-β production by infected macrophages, as previously reported14 (Fig. 5A). Interestingly, treatment of cultures with RvD1 was not able to further increase TGF-β levels in this in vitro system (Fig. 5A). Furthermore, we found no differential induction of arginase activity and TNF-α expression in cultures treated with RvD1 (data not shown).


Resolvin D1 drives establishment of Leishmania amazonensis infection
RvD1 induces the HO-1 production in L. amazonensis-infected human macrophages.Supernatants from infected macrophages were collected after 24 h post infection and evaluated for the levels of transforming growth factor β (TGF-β; A) whereas hemoxygenase-1 (HO-1; B) protein expression was assessed in cell extracts as described in Methods. 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

f5: RvD1 induces the HO-1 production in L. amazonensis-infected human macrophages.Supernatants from infected macrophages were collected after 24 h post infection and evaluated for the levels of transforming growth factor β (TGF-β; A) whereas hemoxygenase-1 (HO-1; B) protein expression was assessed in cell extracts as described in Methods. Data shown are mean and SE of one representative out two independent experiments. *P < 0.05, **P < 0.01.
Mentions: It is well established that induction of cytokines is a critical evasion mechanism used by Leishmania parasites1013. Here, we confirmed that L. amazonensis infection induces TGF-β production by infected macrophages, as previously reported14 (Fig. 5A). Interestingly, treatment of cultures with RvD1 was not able to further increase TGF-β levels in this in vitro system (Fig. 5A). Furthermore, we found no differential induction of arginase activity and TNF-α expression in cultures treated with RvD1 (data not shown).

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