Impact of Leishmania Metalloprotease GP63 on Macrophage Signalling
Several Leishmania surface molecules are known to be important virulence factors. For instance, LPG is recognized as one of the key virulence factor for Leishmania. Interestingly, recent findings permit to believe that the Leishmania GP63 could be also a critical one. GP63 is a metalloprotease found...
Main Authors: | , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2012-05-01
|
Series: | Frontiers in Cellular and Infection Microbiology |
Subjects: | |
Online Access: | http://journal.frontiersin.org/Journal/10.3389/fcimb.2012.00072/full |
id |
doaj-90b4d07b49f24d7980408c764454af04 |
---|---|
record_format |
Article |
spelling |
doaj-90b4d07b49f24d7980408c764454af042020-11-24T23:24:05ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882012-05-01210.3389/fcimb.2012.0007224506Impact of Leishmania Metalloprotease GP63 on Macrophage SignallingAmandine eIsnard0Marina Tiemi Shio1Martin eOlivier2McGill UniversityMcGill UniversityMcGill UniversitySeveral Leishmania surface molecules are known to be important virulence factors. For instance, LPG is recognized as one of the key virulence factor for Leishmania. Interestingly, recent findings permit to believe that the Leishmania GP63 could be also a critical one. GP63 is a metalloprotease found in all Leishmania species under different forms going from membrane-bound to extracellularly secreted ones. Even before parasite entries into the host macrophage, GP63 provides parasite resistance to the complement-mediated lysis and facilitate promastigote engulfment by macrophages. Additionally, it has been found that the degradation of proteins from the macrophage extracellular matrix by GP63 could confer protection to promastigotes, as well as amastigotes, during their initial interaction with the host cell. More recently, GP63 has been observed to rapidly enter within the host macrophage -in part via lipid raft microdomains- and to be pivotal for the subversion of host innate immune response. For instance, it has been found to be responsible for the activation of negative regulatory mechanisms involving activation of protein tyrosine phosphatases (PTPs; SHP-1, PTP1B and TCPTP) that lead to the alteration of several key signalling pathways utilizing JAK and MAP kinases family members, as well as the pivotal IRAK-1 kinase for toll like-dependent signalling. In addition, it has been recently reported that inactivation of some transcription factors such as AP-1 occurs directly in the nuclear environment of the infected cells, and to involve the cleavage and degradation of c-jun and c-fos family members by GP63. Altogether, this signalling inactivation under the mediation of GP63 concurs to inhibit important antimicrobial actions usually under the regulation of the innate immune response, and therefore favouring the survival and propagation of the parasite once into its host intracellular environment.http://journal.frontiersin.org/Journal/10.3389/fcimb.2012.00072/fullLeishmaniahost-pathogen interactioninnate immunitysignallingmacrophageGP63 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Amandine eIsnard Marina Tiemi Shio Martin eOlivier |
spellingShingle |
Amandine eIsnard Marina Tiemi Shio Martin eOlivier Impact of Leishmania Metalloprotease GP63 on Macrophage Signalling Frontiers in Cellular and Infection Microbiology Leishmania host-pathogen interaction innate immunity signalling macrophage GP63 |
author_facet |
Amandine eIsnard Marina Tiemi Shio Martin eOlivier |
author_sort |
Amandine eIsnard |
title |
Impact of Leishmania Metalloprotease GP63 on Macrophage Signalling |
title_short |
Impact of Leishmania Metalloprotease GP63 on Macrophage Signalling |
title_full |
Impact of Leishmania Metalloprotease GP63 on Macrophage Signalling |
title_fullStr |
Impact of Leishmania Metalloprotease GP63 on Macrophage Signalling |
title_full_unstemmed |
Impact of Leishmania Metalloprotease GP63 on Macrophage Signalling |
title_sort |
impact of leishmania metalloprotease gp63 on macrophage signalling |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular and Infection Microbiology |
issn |
2235-2988 |
publishDate |
2012-05-01 |
description |
Several Leishmania surface molecules are known to be important virulence factors. For instance, LPG is recognized as one of the key virulence factor for Leishmania. Interestingly, recent findings permit to believe that the Leishmania GP63 could be also a critical one. GP63 is a metalloprotease found in all Leishmania species under different forms going from membrane-bound to extracellularly secreted ones. Even before parasite entries into the host macrophage, GP63 provides parasite resistance to the complement-mediated lysis and facilitate promastigote engulfment by macrophages. Additionally, it has been found that the degradation of proteins from the macrophage extracellular matrix by GP63 could confer protection to promastigotes, as well as amastigotes, during their initial interaction with the host cell. More recently, GP63 has been observed to rapidly enter within the host macrophage -in part via lipid raft microdomains- and to be pivotal for the subversion of host innate immune response. For instance, it has been found to be responsible for the activation of negative regulatory mechanisms involving activation of protein tyrosine phosphatases (PTPs; SHP-1, PTP1B and TCPTP) that lead to the alteration of several key signalling pathways utilizing JAK and MAP kinases family members, as well as the pivotal IRAK-1 kinase for toll like-dependent signalling. In addition, it has been recently reported that inactivation of some transcription factors such as AP-1 occurs directly in the nuclear environment of the infected cells, and to involve the cleavage and degradation of c-jun and c-fos family members by GP63. Altogether, this signalling inactivation under the mediation of GP63 concurs to inhibit important antimicrobial actions usually under the regulation of the innate immune response, and therefore favouring the survival and propagation of the parasite once into its host intracellular environment. |
topic |
Leishmania host-pathogen interaction innate immunity signalling macrophage GP63 |
url |
http://journal.frontiersin.org/Journal/10.3389/fcimb.2012.00072/full |
work_keys_str_mv |
AT amandineeisnard impactofleishmaniametalloproteasegp63onmacrophagesignalling AT marinatiemishio impactofleishmaniametalloproteasegp63onmacrophagesignalling AT martineolivier impactofleishmaniametalloproteasegp63onmacrophagesignalling |
_version_ |
1725561962109075456 |