The role of Leishmania GP63 in the modulation of innate inflammatory response to Leishmania major infection.
Animals
Computational Biology
Exosomes
/ metabolism
Female
Host-Parasite Interactions
/ physiology
Inflammation
/ immunology
Leishmania
Leishmania major
/ metabolism
Leishmaniasis
/ immunology
Leishmaniasis, Cutaneous
/ immunology
Metalloendopeptidases
/ chemistry
Metalloproteases
/ metabolism
Mice
Mice, Inbred C57BL
Microscopy, Electron, Transmission
Nanoparticles
/ chemistry
Proteomics
/ methods
RNA-Seq
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2021
2021
Historique:
received:
05
08
2021
accepted:
16
12
2021
entrez:
31
12
2021
pubmed:
1
1
2022
medline:
19
1
2022
Statut:
epublish
Résumé
Leishmaniasis is a disease caused by the protozoan parasite Leishmania and is known to affect millions of individuals worldwide. In recent years, we have established the critical role played by Leishmania zinc-metalloprotease GP63 in the modulation of host macrophage signalling and functions, favouring its survival and progression within its host. Leishmania major lacking GP63 was reported to cause limited infection in mice, however, it is still unclear how GP63 may influence the innate inflammatory response and parasite survival in an in vivo context. Therefore, we were interested in analyzing the early innate inflammatory events upon Leishmania inoculation within mice and establish whether Leishmania GP63 influences this initial inflammatory response. Experimentally, L. major WT (L. majorWT), L. major GP63 knockout (L. majorKO), or L. major GP63 rescue (L. majorR) were intraperitoneally inoculated in mice and the inflammatory cells recruited were characterized microscopically and by flow cytometry (number and cell type), and their infection determined. Pro-inflammatory markers such as cytokines, chemokines, and extracellular vesicles (EVs, e.g. exosomes) were monitored and proteomic analysis was performed on exosome contents. Data obtained from this study suggest that Leishmania GP63 does not significantly influence the pathogen-induced inflammatory cell recruitment, but rather their activation status and effector function. Concordantly, internalization of promastigotes during early infection could be influenced by GP63 as fewer L. majorKO amastigotes were found within host cells and appear to maintain in host cells over time. Collectively this study provides a clear analysis of innate inflammatory events occurring during L. major infection and further establish the prominent role of the virulence factor GP63 to provide favourable conditions for host cell infection.
Identifiants
pubmed: 34972189
doi: 10.1371/journal.pone.0262158
pii: PONE-D-21-25358
pmc: PMC8719666
doi:
Substances chimiques
Metalloproteases
EC 3.4.-
Metalloendopeptidases
EC 3.4.24.-
glycoprotein gp63, Leishmania
EC 3.4.24.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0262158Subventions
Organisme : CIHR
ID : PJT-159765
Pays : Canada
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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