The role of metalloproteases in<i>Leishmania</i>species infection in the New World: a systematic review

Murase, Letícia Sayuri; Souza, João Vítor Perez de; Neto, Quirino Alves de Lima; Mello, Tatiane França Perles de; Cardoso, Bruna Muller; Lera‐Nonose, Daniele Stéfanie Sara Lopes; Teixeira, Jorge Juarez Vieira; Lonardoni, Maria Valdrinez Campana; Demarchi, Izabel Galhardo

doi:10.1017/s0031182018000367

Cited by 17 publications

(14 citation statements)

References 42 publications

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“…Thus, the ciliates must be able to resist the attack from the fish immune system and also to destroy fish tissue, for which proteases may be important. In the present study, we observed an increase in the expression of several genes of the leishmanolysin family, which are membrane-bound metalloproteases capable of degrading and cleaving many biological molecules [ 39 ]. Leishmanolysin GP63 is a major surface protein and is considered one of the main virulence factors in the human pathogen Leishmania [ 40 ].…”

Section: Discussionmentioning

confidence: 95%

Interactions between the Parasite Philasterides dicentrarchi and the Immune System of the Turbot Scophthalmus maximus. A Transcriptomic Analysis

Valle

Leiro

Pereiro

et al. 2020

Biology

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The present study analyses the interactions between Philasterides dicentrarchi (a ciliate parasite that causes high mortalities in cultured flatfish) and the peritoneal cells of the turbot Scophthalmus maximus during an experimental infection. The transcriptomic response was evaluated in the parasites and in the fish peritoneal cells, at 1, 2 and 4 h post-infection (hpi) in turbot injected intraperitoneally (ip) with 107 ciliates and at 12 and 48 hpi in turbot injected ip with 105 ciliates. Numerous genes were differentially expressed (DE) in P. dicentrarchi, relative to their expression in control ciliates (0 hpi): 407 (369 were up-regulated) at 1 hpi, 769 (415 were up-regulated) at 2 hpi and 507 (119 were up-regulated) at 4 hpi. Gene ontology (GO) analysis of the DE genes showed that the most representative categories of biological processes affected at 1, 2 and 4 hpi were biosynthetic processes, catabolic processes, biogenesis, proteolysis and transmembrane transport. Twelve genes of the ABC transporter family and eight genes of the leishmanolysin family were DE at 1, 2 and 4 hpi. Most of these genes were strongly up-regulated (UR), suggesting that they are involved in P. dicentrarchi infection. A third group of UR genes included several genes related to ribosome biogenesis, DNA transcription and RNA translation. However, expression of tubulins and tubulin associated proteins, such as kinesins or dyneins, which play key roles in ciliate division and movement, was down-regulated (DR). Similarly, genes that coded for lysosomal proteins or that participate in the cell cycle mitotic control, glycolysis, the Krebs cycle and/or in the electron transport chain were also DR. The transcriptomic analysis also revealed that in contrast to many parasites, which passively evade the host immune system, P. dicentrarchi strongly stimulated turbot peritoneal cells. Many genes related to inflammation were DE in peritoneal cells at 1, 2 and 4 hpi. However, the response was much lower at 12 hpi and almost disappeared completely at 48 hpi in fish that were able to kill P. dicentrarchi during the first few hpi. The genes that were DE at 1, 2 and 4 hpi were mainly related to the apoptotic process, the immune response, the Fc-epsilon receptor signalling pathway, the innate immune response, cell adhesion, cell surface receptors, the NF-kappaB signalling pathway and the MAPK cascade. Expression of toll-like receptors 2, 5 and 13 and of several components of NF-κB, MAPK and JAK/STAT signalling pathways was UR in the turbot peritoneal cells. Genes expressing chemokines and chemokine receptors, genes involved in prostaglandin and leukotriene synthesis, prostaglandins, leukotriene receptors, proinflammatory cytokines and genes involved in apoptosis were strongly UR during the first four hours of infection. However, expression of anti-inflammatory cytokines such as Il-10 and lipoxygenases with anti-inflammatory activity (i.e., arachidonate 15-lipoxygenase) were only UR at 12 and/or 48 hpi, indicating an anti-inflammatory state in these groups of fish. In conclusion, the present study shows the regulation of several genes in P. dicentrarchi during the early stages of infection, some of which probably play important roles in this process. The infection induced a potent acute inflammatory response, and many inflammatory genes were regulated in peritoneal cells, showing that the turbot uses all the protective mechanisms it has available to prevent the entry of the parasite.

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Section: Discussionmentioning

confidence: 95%

Interactions between the Parasite Philasterides dicentrarchi and the Immune System of the Turbot Scophthalmus maximus. A Transcriptomic Analysis

Valle

Leiro

Pereiro

et al. 2020

Biology

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“…MSP proteins are known to play important roles in parasite virulence and in the pathogenesis of infections caused by Kinetoplastida [43]. In Leishmania spp., the MSP is called GP63 (63 kDa glycoprotein), a class of zinc metalloproteases abundant on the surface of the parasite, and one of the enzymes best studied and characterized in this parasite [44].…”

Section: Major Surface Proteases From Trypanosoma Brucei: An Impormentioning

confidence: 99%

“…In general, T. brucei metalloprotease is responsible for the degradation of proteins of the blood–brain barrier, such as collagen and laminin, which is possibly pivotal at the transition phase and hemolymphatic phase, to meningoencephalitis [53]. When the expression of the GPI–PLC enzyme in the procyclic forms of T. brucei occurs, the release of VSG is ensured by the constant expression of the MSP enzyme [20,44].…”

Section: Contribution Of the Plc Enzyme In The Removal Of Vsg On Tmentioning

confidence: 99%

Trypanosoma brucei Interaction with Host: Mechanism of VSG Release as Target for Drug Discovery for African Trypanosomiasis

Moreno

Temporão

Torres

et al. 2019

IJMS

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The protozoan Trypanosoma brucei, responsible for animal and human trypanosomiasis, has a family of major surface proteases (MSPs) and phospholipase-C (PLC), both involved in some mechanisms of virulence during mammalian infections. During parasitism in the mammalian host, this protozoan is exclusively extracellular and presents a robust mechanism of antigenic variation that allows the persistence of infection. There has been incredible progress in our understanding of how variable surface glycoproteins (VSGs) are organised and expressed, and how expression is switched, particularly through recombination. The objective of this manuscript is to create a reflection about the mechanisms of antigenic variation in T. brucei, more specifically, in the process of variable surface glycoprotein (VSG) release. We firstly explore the mechanism of VSG release as a potential pathway and target for the development of anti-T. brucei drugs.

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“…The degree of pathogen or tissue leukocyte-driven proteolytic cleavage will regulate the degree of degradation vs. liberation of cleaved CCL7 with antagonist activity (16, 18). Indeed, the Leishmania metalloprotease GP63 is an extensively studied parasite virulence factor (60) and could directly alter chemokine activity. Competition between chemokines in the milieu for binding chemokine receptors and/or glycosaminoglycans (GAGs) may also regulate net chemotactic activity in the infected tissue.…”

Section: Discussionmentioning

confidence: 99%

CCL7 Is a Negative Regulator of Cutaneous Inflammation Following Leishmania major Infection

et al. 2019

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The chemokine CCL7 (MCP3) is known to promote the recruitment of many innate immune cell types including monocytes and neutrophils to sites of bacterial and viral infection and eosinophils and basophils to sites of allergic inflammation. CCL7 upregulation has been associated with many inflammatory settings including infection, cardiovascular disease, and the tumor microenvironment. CCL7's pleotropic effects are due in part to its ability to bind numerous chemokine receptors, namely CCR1, CCR2, CCR3, CCR5, and CCR10. CCL7-blockade or CCL7-deficiency is often marked by decreased inflammation and poor pathogen control. In the context of Leishmania major infection, CCL7 is specifically upregulated in the skin one-2 weeks after infection but its role in L. major control is unclear. To determine CCL7's impact on the response to L. major we infected WT and CCL7−/− C57BL/6 mice. L. major infection of CCL7-deficient mice led to an unexpected increase in inflammation in the infected skin 2 weeks post-infection. A broad increase in immune cell subsets was observed but was dominated by enhanced neutrophilic infiltration. Increased neutrophil recruitment was associated with an enhanced IL-17 gene profile in the infected skin. CCL7 was shown to directly antagonize neutrophil migration in vitro and CCL7 add-back in vivo specifically reduced neutrophil influx into the infected skin revealing an unexpected role for CCL7 in limiting neutrophil recruitment during L. major infection. Enhanced neutrophilic infiltration in CCL7-deficient mice changed the balance of L. major infected host cells with an increase in the ratio of infected neutrophils over monocytes/macrophages. To determine the consequence of CCL7 deficiency on L. major control we analyzed parasite load cutaneously at the site of infection and viscerally in the draining LN and spleen. The CCL7−/− mice supported robust cutaneous parasite control similar to their WT C57BL/6 counterparts. In contrast, CCL7-deficiency led to greater parasite dissemination and poor parasite control in the spleen. Our studies reveal a novel role for CCL7 in negatively regulating cutaneous inflammation, specifically neutrophils, early during L. major infection. We propose that CCL7-mediated dampening of the early immune response in the skin may limit the ability of the parasite to disseminate without compromising cutaneous control.

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The role of metalloproteases inLeishmaniaspecies infection in the New World: a systematic review

Cited by 17 publications

References 42 publications

Interactions between the Parasite Philasterides dicentrarchi and the Immune System of the Turbot Scophthalmus maximus. A Transcriptomic Analysis

Interactions between the Parasite Philasterides dicentrarchi and the Immune System of the Turbot Scophthalmus maximus. A Transcriptomic Analysis

Trypanosoma brucei Interaction with Host: Mechanism of VSG Release as Target for Drug Discovery for African Trypanosomiasis

CCL7 Is a Negative Regulator of Cutaneous Inflammation Following Leishmania major Infection

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