Leishmania model for microbial virulence: the relevance of parasite multiplication and pathoantigenicity

Chang, Kwang-Poo; Reed, Steven G.; McGwire, Bradford S.; Soong, Lynn

doi:10.1016/s0001-706x(02)00238-3

Cited by 121 publications

(99 citation statements)

References 78 publications

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“…The downregulation of activations markers by parasites was described by several authors and is thought to be an essential component of the Leishmania immunomodulatory arsenal [5,26]. Ultimately the DCs recruitment to the infection site and their subsequent deactivation might lead to an adaptive immune response delay, giving the parasite enough time to either escape the inoculation site inside a permissive phagocytic cell or create a privileged niche that enables a silent progression of infection [60,61]. …”

Section: Discussionmentioning

confidence: 99%

More than just exosomes: distinct Leishmania infantum extracellular products potentiate the establishment of infection

Pérez-Cabezas

Cecílio

Silva

et al. 2018

J of Extracellular Vesicle

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The use of secretion pathways for effector molecule delivery by microorganisms is a trademark of pathogenesis. Leishmania extracellular vesicles (EVs) were shown to have significant immunomodulatory potential. Still, they will act in conjunction with other released parasite-derived products that might modify the EVs effects. Notwithstanding, the immunomodulatory properties of these non-vesicular components and their influence in the infectious process remains unknown. To address this, we explored both in vitro and in vivo the immunomodulatory potential of promastigotes extracellular material (EXO), obtained as a whole or separated in two different fractions: EVs or vesicle depleted EXO (VDE). Using an air pouch model, we observed that EVs and VDE induced a dose-dependent cell recruitment profile different from the one obtained with parasites, attracting significantly fewer neutrophils and more dendritic cells (DCs). Additionally, when we co-inoculated parasites with extracellular products a drop in cell recruitment was observed. Moreover, in vitro, while VDE (but not EVs) downregulated the expression of DCs and macrophages activation markers, both products were able to diminish the responsiveness of these cells to LPS. Finally, the presence of Leishmania infantum extracellular products in the inoculum promoted a dose-dependent infection potentiation in vivo, highlighting their relevance for the infectious process. In conclusion, our data demonstrate that EVs are not the only relevant players among the parasite exogenous products. This, together with the dose-dependency observed, opens new avenues to the comprehension of Leishmania infectious process. The approach presented here should be exploited to revisit existing data and considered for future studies in other infection models.

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Section: Discussionmentioning

confidence: 99%

More than just exosomes: distinct Leishmania infantum extracellular products potentiate the establishment of infection

Pérez-Cabezas

Cecílio

Silva

et al. 2018

J of Extracellular Vesicle

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“…Thus, the addition of KMP-11 to the cultures was simply an amplification of something that occurs spontaneously during infection. The extracellular presence of KMP-11 in the supernatants of the Leishmaniainfected macrophage cultures is possibly a result of amastigote killing and lysis of parasitised macrophages (Chang et al 2003). The generation of KMP-11-defficient mutants could help to determine the importance of this molecule for L. amazonensis infection.…”

Section: Discussionmentioning

confidence: 99%

Kinetoplastid membrane protein-11 exacerbates infection with Leishmania amazonensis in murine macrophages

Lacerda

Cysne-Finkelstein

Nunes

et al. 2012

Mem. Inst. Oswaldo Cruz

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In Leishmania amazonensis, kinetoplastid membrane protein-11 (KMP-11) expression increases during metacyclogenesis and is higher in amastigotes than in promastigotes, suggesting a role for this protein in the infection of the mammalian host. We show that the addition of KMP-11 exacerbates L. amazonensis infection in peritoneal macrophages from BALB/c mice by increasing interleukin (IL)-10 secretion and arginase activity while reducing nitric oxide (NO) production. The doses of KMP-11, the IL-10 levels and the intracellular amastigote loads were strongly, positively and significantly correlated. The increase in parasite load induced by KMP-11 was inhibited by anti-KMP-11 or anti-IL-10 neutralising antibodies, but not by isotype controls. The neutralising antibodies, but not the isotype controls, were also able to significantly decrease the parasite load in macrophages cultured without the addition of KMP-11, demonstrating that KMP-11-induced exacerbation of the infection is not dependent on the addition of exogenous KMP-11 and that the protein naturally expressed by the parasite is able to promote it. In this study, the exacerbating effect of KMP-11 on macrophage infection with Leishmania is for the first time demonstrated, implicating it as a virulence factor in L. amazonensis. The stimulation of IL-10 production and arginase activity and the inhibition of NO synthesis are likely involved in this effect

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“…The NdK released by Leishmania apparently have functional importance as one of the invasive/ evasive determinants crucial for the successful infection of macrophages [54], i. e. decreasing eATP to preserve the integrity of their host cells. Immune cells are thought to release ATP when killed, injured or under stress, leading to its local accumulation in significant amounts at the site of inflammation [12,13].…”

Section: Discussionmentioning

confidence: 99%

Leishmania-released nucleoside diphosphate kinase prevents ATP-mediated cytolysis of macrophages

Kolli

Košťál

Zaborina

et al. 2008

Molecular and Biochemical Parasitology

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Leishmania amazonensis was found to release nucleoside diphosphate kinase (NdK) -a stable enzyme capable of decreasing extracellular ATP. The release of this enzyme from Leishmania results in its progressive accumulation extracellularly as they replicate, peaking at the stationary phase in vitro. The released NdK is immunoprecipitable and constitutes ~40% of its total activities and proteins. The retention of a known cytosolic protein by wild type cells and a fluorescent protein by DsRed transfectants at stationary phase, which release NdK, indicates that this is a spontaneous event, independent of inadvertent cytolysis. Recombinant products of Leishmania NdK prepared were enzymatically and immunologically active. Both recombinant and native Leishmania NdK utilized ATP to produce expected nucleoside triphosphates in the presence of nucleoside diphosphates in excess. Both native and recombinant Leishmania NdK were also found to prevent ATP-induced cytolysis of J774 macrophages in vitro, as determined by assays for lactate dehydrogenase release from these cells and for their mitochondrial membrane potential changes. The results obtained thus suggest that Leishmania NdK not only serves its normal house-keeping and other important functions true to all cells, but also prevents ATP-mediated lysis of macrophages, thereby preserving the integrity of the host cells to the benefit of the parasite.

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Leishmania model for microbial virulence: the relevance of parasite multiplication and pathoantigenicity

Cited by 121 publications

References 78 publications

More than just exosomes: distinct Leishmania infantum extracellular products potentiate the establishment of infection

More than just exosomes: distinct Leishmania infantum extracellular products potentiate the establishment of infection

Kinetoplastid membrane protein-11 exacerbates infection with Leishmania amazonensis in murine macrophages

Leishmania-released nucleoside diphosphate kinase prevents ATP-mediated cytolysis of macrophages

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