A comparison of two distinct murine macrophage gene expression profiles in response to Leishmania amazonensisinfection

Probst, Christian M.; Silva, Rodrigo A; Menezes, Juliana Perrone Bezerra de; Almeida, Taís Fontoura de; Gomes, Ivana Nunes; Dallabona, Andréia C; Ozaki, Luiz Shozo; Buck, Gregory A.; Pavoni, Daniela Parada; Krieger, Marco Aurélio; Veras, Patrícia Sampaio Tavares

doi:10.1186/1471-2180-12-22

Cited by 23 publications

(39 citation statements)

References 50 publications

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“…We then hypothesized that the mechanisms linking macrophage exposure to RvD1 and enhanced intracellular parasite replication could involve subversion of anti-parasite macrophage effector functions. During the Leishmania infection, it is well established that parasite can present a series of escape mechanisms, such the deactivation of macrophages23, induction of antioxidants1115 and anti-inflammatory cytokines, such TGB-β14. In other experimental models, resolvins have been shown to induce high levels of TGF-β, increasing phagocytosis of cells by macrophages and inducing an anti-inflammatory phenotype24.…”

Section: Discussionmentioning

confidence: 99%

Resolvin D1 drives establishment of Leishmania amazonensis infection

Malta‐Santos

Andrade²,

Zanette

et al. 2017

Sci Rep

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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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Section: Discussionmentioning

confidence: 99%

Resolvin D1 drives establishment of Leishmania amazonensis infection

Malta‐Santos

Andrade²,

Zanette

et al. 2017

Sci Rep

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“…Furthermore, immunoproteomics efforts focused on evaluating responses to defined parasite T-cell epitopes as vaccine/diagnostic targets. These approaches have also expanded the understanding of the array of events involved in Leishmania infection [ 86 , 87 ]. The construction of an index map for a large number of Leishmania species is another large-scale approach that was exploited by several authors and contributed to a better understanding of the biology of this parasite, aiming to identify and locate as many parasite proteins as possible [ 21 , 101 ].…”

Section: High-throughput Screening For New Targetsmentioning

confidence: 99%

Advances in Development of New Treatment for Leishmaniasis

Menezes

Guedes

Petersen

et al. 2015

BioMed Research International

158

113

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Leishmaniasis is a neglected infectious disease caused by several different species of protozoan parasites of the genus Leishmania. Current strategies to control this disease are mainly based on chemotherapy. Despite being available for the last 70 years, leishmanial chemotherapy has lack of efficiency, since its route of administration is difficult and it can cause serious side effects, which results in the emergence of resistant cases. The medical-scientific community is facing difficulties to overcome these problems with new suitable and efficient drugs, as well as the identification of new drug targets. The availability of the complete genome sequence of Leishmania has given the scientific community the possibility of large-scale analysis, which may lead to better understanding of parasite biology and consequent identification of novel drug targets. In this review we focus on how high-throughput analysis is helping us and other groups to identify novel targets for chemotherapeutic interventions. We further discuss recent data produced by our group regarding the use of the high-throughput techniques and how this helped us to identify and assess the potential of new identified targets.

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“…Many additional mouse strains are susceptible to L . amazonensis , in particular, the CBA strain, which develops severe lesions in comparison to C57BL/6, presenting small chronic lesions [ 56 ]. An advantage of the C57BL/6 mouse is the large number of gene knockout lines in the C57BL/6 background that can be used to address important questions such as the contribution of a specific immune response to drug efficacy.…”

Section: New World: L Mexicanamentioning

confidence: 99%

A Review: The Current In Vivo Models for the Discovery and Utility of New Anti-leishmanial Drugs Targeting Cutaneous Leishmaniasis

et al. 2015

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The current in vivo models for the utility and discovery of new potential anti-leishmanial drugs targeting Cutaneous Leishmaniasis (CL) differ vastly in their immunological responses to the disease and clinical presentation of symptoms. Animal models that show similarities to the human form of CL after infection with Leishmania should be more representative as to the effect of the parasite within a human. Thus, these models are used to evaluate the efficacy of new anti-leishmanial compounds before human clinical trials. Current animal models aim to investigate (i) host–parasite interactions, (ii) pathogenesis, (iii) biochemical changes/pathways, (iv) in vivo maintenance of parasites, and (v) clinical evaluation of drug candidates. This review focuses on the trends of infection observed between Leishmania parasites, the predictability of different strains, and the determination of parasite load. These factors were used to investigate the overall effectiveness of the current animal models. The main aim was to assess the efficacy and limitations of the various CL models and their potential for drug discovery and evaluation. In conclusion, we found that the following models are the most suitable for the assessment of anti-leishmanial drugs: L. major–C57BL/6 mice (or–vervet monkey, or–rhesus monkeys), L. tropica–CsS-16 mice, L. amazonensis–CBA mice, L. braziliensis–golden hamster (or–rhesus monkey). We also provide in-depth guidance for which models are not suitable for these investigations.

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A comparison of two distinct murine macrophage gene expression profiles in response to Leishmania amazonensisinfection

Cited by 23 publications

References 50 publications

Resolvin D1 drives establishment of Leishmania amazonensis infection

Resolvin D1 drives establishment of Leishmania amazonensis infection

Advances in Development of New Treatment for Leishmaniasis

A Review: The Current In Vivo Models for the Discovery and Utility of New Anti-leishmanial Drugs Targeting Cutaneous Leishmaniasis

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