The immunobiology of Leishmania braziliensis infection

Oliveira, Camila I. de; Brodskyn, Cláudia

doi:10.3389/fimmu.2012.00145

Cited by 61 publications

(55 citation statements)

References 88 publications

(105 reference statements)

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“…in [1]). A hallmark feature of the immunological response in localized CL is a strong Th1 type immune response to soluble Leishmania antigen (SLA), demonstrated by a positive delayed type hypersensitivity (DTH) reaction to the Leishmania skin test, as well as lymphocyte proliferation and high levels of IFN-γ and TNF-α [2–4].…”

Section: Introductionmentioning

confidence: 99%

Gene Expression Profile of High IFN-γ Producers Stimulated with Leishmania braziliensis Identifies Genes Associated with Cutaneous Leishmaniasis

et al. 2016

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BackgroundThe initial response to Leishmania parasites is essential in determining disease development or resistance. In vitro, a divergent response to Leishmania, characterized by high or low IFN-γ production has been described as a potential tool to predict both vaccine response and disease susceptibility in vivo.Methods and findingsWe identified uninfected and healthy individuals that were shown to be either high- or low IFN-γ producers (HPs and LPs, respectively) following stimulation of peripheral blood cells with Leishmania braziliensis. Following stimulation, RNA was processed for gene expression analysis using immune gene arrays. Both HPs and LPs were shown to upregulate the expression of CXCL10, IFI27, IL6 and LTA. Genes expressed in HPs only (CCL7, IL8, IFI44L and IL1B) were associated with pathways related to IL17 and TREM 1 signaling. In LPs, uniquely expressed genes (for example IL9, IFI44, IFIT1 and IL2RA) were associated with pathways related to pattern recognition receptors and interferon signaling. We then investigated whether the unique gene expression profiles described here could be recapitulated in vivo, in individuals with active Cutaneous Leishmaniasis or with subclinical infection. Indeed, using a set of six genes (TLR2, JAK2, IFI27, IFIT1, IRF1 and IL6) modulated in HPs and LPs, we could successfully discriminate these two clinical groups. Finally, we demonstrate that these six genes are significantly overexpressed in CL lesions.ConclusionUpon interrogation of the peripheral response of naive individuals with diverging IFN-γ production to L. braziliensis, we identified differences in the innate response to the parasite that are recapitulated in vivo and that discriminate CL patients from individuals presenting a subclinical infection.

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Section: Introductionmentioning

confidence: 99%

Gene Expression Profile of High IFN-γ Producers Stimulated with Leishmania braziliensis Identifies Genes Associated with Cutaneous Leishmaniasis

et al. 2016

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“…5 Nowadays, leishmaniasis is largely moving towards domestic habitats, 6,7 resulting in a marked MCL-incidence rise in Europe. 8,9 Although there are no standardized protocols for the treatment of MCL, 10 the World Health Organization recommends the use of intravenous pentavalent antimony and its derived molecules: sodium stibogluconate and meglumine antimoniate. 11 Their killing mechanism is not known, and they are effective only on the intracellular formsthe amastigotes.…”

Section: Introductionmentioning

confidence: 99%

Enhanced photodynamic leishmanicidal activity of hydrophobic zinc phthalocyanine within archaeolipids containing liposomes

Perez

Casasco

Schilrreff

et al. 2014

IJN

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In this work, the in vitro anti-Leishmania activity of photodynamic liposomes made of soybean phosphatidylcholine, sodium cholate, total polar archaeolipids (TPAs) extracted from the hyperhalophile archaea Halorubrum tebenquichense and the photosensitizer zinc phthalocyanine (ZnPcAL) was compared to that of ultradeformable photodynamic liposomes lacking TPAs (ZnPcUDLs). We found that while ZnPcUDLs and ZnPcALs (130 nm mean diameter and −35 mV zeta potential) were innocuous against promastigotes, a low concentration (0.01 µM ZnPc and 7.6 µM phospholipids) of ZnPcALs irradiated at a very low-energy density (0.2 J/cm 2 ) eliminated L. braziliensis amastigotes from J774 macrophages, without reducing the viability of the host cells. In such conditions, ZnPcALs were harmless for J774 macrophages, HaCaT keratinocytes, and bone marrow-derived dendritic cells. Therefore, topical photodynamic treatment would not likely affect skin-associated lymphoid tissue. ZnPcALs were extensively captured by macrophages, but ZnPcUDLs were not, leading to 2.5-fold increased intracellular delivery of ZnPc than with ZnPcUDLs. Despite mediating low levels of reactive oxygen species, the higher delivery of ZnPc and the multiple (caveolin-and clathrin-dependent plus phagocytic) intracellular pathway followed by ZnPc would have been the reason for the higher antiamastigote activity of ZnPcALs. The leishmanicidal activity of photodynamic liposomal ZnPc was improved by TPA-containing liposomes.

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“…Just as the anti-inflammatory milieu elicited by apoptotic cells enhances leishmanial growth, 22 Leishmania themselves also lead to the induction of antiinflammatory cytokines in infected mammalian hosts. 23 Among these, it is striking that TGFβ, in addition to suppressing host inflammatory responses, also serves as a stimulus for leishmanial growth. 24 Especially under conditions of chronic Leishmania infection, systemic cytokine profiles in infected individuals resemble the apoptotic-like anti-inflammatory state.…”

Section: Open Questionsmentioning

confidence: 99%

“…24 Especially under conditions of chronic Leishmania infection, systemic cytokine profiles in infected individuals resemble the apoptotic-like anti-inflammatory state. 23 However, the specific triggering mechanism for antiinflammatory cytokine expression has not been elucidated.…”

Section: Open Questionsmentioning

confidence: 99%

Exploiting death: apoptotic immunity in microbial pathogenesis

Ucker

2016

Cell Death Differ

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Innate immunity typically is responsible for initial host responses against infections. Independently, nucleated cells that die normally as part of the physiological process of homeostasis in mammals (including humans) suppress immunity. Specifically, the physiological process of cell death (apoptosis) generates cells that are recognized specifically by viable cells of all types and elicit a profound transient suppression of host immunity (termed 'innate apoptotic immunity' (IAI)). IAI appears to be important normally for the maintenance of self-tolerance and for the resolution of inflammation. In addition, pathogens are able to take advantage of IAI through a variety of distinct mechanisms, to enable their proliferation within the host and enhance pathogenicity. For example, the protist pathogen Leishmania amazonensis, at its infective stage, mimics apoptotic cells by expressing apoptotic-like protein determinants on the cell surface, triggering immunosuppression directly. In contrast, the pathogenic bacterium Listeria monocytogenes triggers cell death in host lymphocytes, relying on those apoptotic cells to suppress host immune control and facilitate bacterial expansion. Finally, although the inhibition of apoptotic cell death is a common attribute of many viruses which facilitates their extended replication, it is clear that adenoviruses also reprogram the non-apoptotic dead cells that arise subsequently to manifest apoptotic-like immunosuppressive properties. These three instances represent diverse strategies used by microbial pathogens to exploit IAI, focusing attention on the potency of this facet of host immune control. Further examination of these cases will be revealing both of varied mechanisms of pathogenesis and the processes involved in IAI control.

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The immunobiology of Leishmania braziliensis infection

Cited by 61 publications

References 88 publications

Gene Expression Profile of High IFN-γ Producers Stimulated with Leishmania braziliensis Identifies Genes Associated with Cutaneous Leishmaniasis

Gene Expression Profile of High IFN-γ Producers Stimulated with Leishmania braziliensis Identifies Genes Associated with Cutaneous Leishmaniasis

Enhanced photodynamic leishmanicidal activity of hydrophobic zinc phthalocyanine within archaeolipids containing liposomes

Exploiting death: apoptotic immunity in microbial pathogenesis

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