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Deception and manipulation: the arms of leishmania, a successful parasite.

Cecílio P, Pérez-Cabezas B, Santarém N, Maciel J, Rodrigues V, Cordeiro da Silva A - Front Immunol (2014)

Bottom Line: As a result of a long host-parasite co-evolutionary process, Leishmania spp. developed different immunomodulatory strategies that are essential for the establishment of infection.The understanding of the mechanisms associated with immune evasion and disease progression is essential for the development of novel therapies and vaccine approaches.Here, we revise how the parasite manipulates cell death and immune responses to survive and thrive in the shadow of the immune system.

View Article: PubMed Central - PubMed

Affiliation: Parasite Disease Group, Institute for Molecular and Cell Biology (IBMC), University of Porto , Porto , Portugal.

ABSTRACT
Leishmania spp. are intracellular parasitic protozoa responsible for a group of neglected tropical diseases, endemic in 98 countries around the world, called leishmaniasis. These parasites have a complex digenetic life cycle requiring a susceptible vertebrate host and a permissive insect vector, which allow their transmission. The clinical manifestations associated with leishmaniasis depend on complex interactions between the parasite and the host immune system. Consequently, leishmaniasis can be manifested as a self-healing cutaneous affliction or a visceral pathology, being the last one fatal in 85-90% of untreated cases. As a result of a long host-parasite co-evolutionary process, Leishmania spp. developed different immunomodulatory strategies that are essential for the establishment of infection. Only through deception and manipulation of the immune system, Leishmania spp. can complete its life cycle and survive. The understanding of the mechanisms associated with immune evasion and disease progression is essential for the development of novel therapies and vaccine approaches. Here, we revise how the parasite manipulates cell death and immune responses to survive and thrive in the shadow of the immune system.

No MeSH data available.


Related in: MedlinePlus

Silent entry of Leishmania into the host cells. Live and dead parasites are engulfed by phagocytes. The recognition of the externalized phosphatidylserine present on the cellular membrane of dead parasites induces TGF-β secretion and TNF-α downregulation (1). Neutrophil apoptosis is delayed by Leishmania (2). Both dendritic cells (3) and macrophages (4) remove neutrophil apoptotic bodies carrying Leishmania promastigotes and secrete TGF-β and IL-10. Macrophages (5) can also phagocyte parasites extruded within other macrophage membrane blebs, which in turn promotes the secretion of IL-10.
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Figure 1: Silent entry of Leishmania into the host cells. Live and dead parasites are engulfed by phagocytes. The recognition of the externalized phosphatidylserine present on the cellular membrane of dead parasites induces TGF-β secretion and TNF-α downregulation (1). Neutrophil apoptosis is delayed by Leishmania (2). Both dendritic cells (3) and macrophages (4) remove neutrophil apoptotic bodies carrying Leishmania promastigotes and secrete TGF-β and IL-10. Macrophages (5) can also phagocyte parasites extruded within other macrophage membrane blebs, which in turn promotes the secretion of IL-10.

Mentions: Parasite cell death, reviewed elsewhere (25–27), seems to be very relevant for the deception of the initial immune response. Some authors described that the presence of apoptotic parasites is essential for successful infection of mice susceptible to cutaneous leishmaniasis. Indeed BALB/c mice did not develop disease after intradermal infection with purified virulent non-apoptotic parasites (28, 29). The need for dead parasites in the infective inoculum is related with the exposure of phosphatidylserine (PS) in the outer leaflet of the parasite cytoplasmic membrane. The exposure of this phospholipid enables a silent invasion, inducing the production of anti-inflammatory cytokines such as TGF-β (30, 31). In fact, a recent study shows that the administration of a PS-targeting antibody after C57Bl/6 mice intradermal infection with L. amazonensis promastigotes renders the animals more resistant to the infection (32). Thereby, and as represented in Figure 1, the inoculation of equal proportions of dead and live parasites in the mammalian host may allow the silent entry of Leishmania into the first cells recruited to the inoculation site (28, 33).


Deception and manipulation: the arms of leishmania, a successful parasite.

Cecílio P, Pérez-Cabezas B, Santarém N, Maciel J, Rodrigues V, Cordeiro da Silva A - Front Immunol (2014)

Silent entry of Leishmania into the host cells. Live and dead parasites are engulfed by phagocytes. The recognition of the externalized phosphatidylserine present on the cellular membrane of dead parasites induces TGF-β secretion and TNF-α downregulation (1). Neutrophil apoptosis is delayed by Leishmania (2). Both dendritic cells (3) and macrophages (4) remove neutrophil apoptotic bodies carrying Leishmania promastigotes and secrete TGF-β and IL-10. Macrophages (5) can also phagocyte parasites extruded within other macrophage membrane blebs, which in turn promotes the secretion of IL-10.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4202772&req=5

Figure 1: Silent entry of Leishmania into the host cells. Live and dead parasites are engulfed by phagocytes. The recognition of the externalized phosphatidylserine present on the cellular membrane of dead parasites induces TGF-β secretion and TNF-α downregulation (1). Neutrophil apoptosis is delayed by Leishmania (2). Both dendritic cells (3) and macrophages (4) remove neutrophil apoptotic bodies carrying Leishmania promastigotes and secrete TGF-β and IL-10. Macrophages (5) can also phagocyte parasites extruded within other macrophage membrane blebs, which in turn promotes the secretion of IL-10.
Mentions: Parasite cell death, reviewed elsewhere (25–27), seems to be very relevant for the deception of the initial immune response. Some authors described that the presence of apoptotic parasites is essential for successful infection of mice susceptible to cutaneous leishmaniasis. Indeed BALB/c mice did not develop disease after intradermal infection with purified virulent non-apoptotic parasites (28, 29). The need for dead parasites in the infective inoculum is related with the exposure of phosphatidylserine (PS) in the outer leaflet of the parasite cytoplasmic membrane. The exposure of this phospholipid enables a silent invasion, inducing the production of anti-inflammatory cytokines such as TGF-β (30, 31). In fact, a recent study shows that the administration of a PS-targeting antibody after C57Bl/6 mice intradermal infection with L. amazonensis promastigotes renders the animals more resistant to the infection (32). Thereby, and as represented in Figure 1, the inoculation of equal proportions of dead and live parasites in the mammalian host may allow the silent entry of Leishmania into the first cells recruited to the inoculation site (28, 33).

Bottom Line: As a result of a long host-parasite co-evolutionary process, Leishmania spp. developed different immunomodulatory strategies that are essential for the establishment of infection.The understanding of the mechanisms associated with immune evasion and disease progression is essential for the development of novel therapies and vaccine approaches.Here, we revise how the parasite manipulates cell death and immune responses to survive and thrive in the shadow of the immune system.

View Article: PubMed Central - PubMed

Affiliation: Parasite Disease Group, Institute for Molecular and Cell Biology (IBMC), University of Porto , Porto , Portugal.

ABSTRACT
Leishmania spp. are intracellular parasitic protozoa responsible for a group of neglected tropical diseases, endemic in 98 countries around the world, called leishmaniasis. These parasites have a complex digenetic life cycle requiring a susceptible vertebrate host and a permissive insect vector, which allow their transmission. The clinical manifestations associated with leishmaniasis depend on complex interactions between the parasite and the host immune system. Consequently, leishmaniasis can be manifested as a self-healing cutaneous affliction or a visceral pathology, being the last one fatal in 85-90% of untreated cases. As a result of a long host-parasite co-evolutionary process, Leishmania spp. developed different immunomodulatory strategies that are essential for the establishment of infection. Only through deception and manipulation of the immune system, Leishmania spp. can complete its life cycle and survive. The understanding of the mechanisms associated with immune evasion and disease progression is essential for the development of novel therapies and vaccine approaches. Here, we revise how the parasite manipulates cell death and immune responses to survive and thrive in the shadow of the immune system.

No MeSH data available.


Related in: MedlinePlus