Cargando…

C-reactive protein binds to short phosphoglycan repeats of Leishmania secreted proteophosphoglycans and activates complement

Human C-reactive protein (CRP) binds to lipophosphoglycan (LPG), a virulence factor of Leishmania spp., through the repeating phosphodisaccharide region. We report here that both major components of promastigote secretory gel (PSG), the filamentous proteophosphoglycan (fPPG) and the secreted acid ph...

Descripción completa

Detalles Bibliográficos
Autores principales: Seow, Eu Shen, Doran, Eve C., Schroeder, Jan-Hendrik, Rogers, Matthew E., Raynes, John G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10500826/
https://www.ncbi.nlm.nih.gov/pubmed/37720216
http://dx.doi.org/10.3389/fimmu.2023.1256205
_version_ 1785105995389730816
author Seow, Eu Shen
Doran, Eve C.
Schroeder, Jan-Hendrik
Rogers, Matthew E.
Raynes, John G.
author_facet Seow, Eu Shen
Doran, Eve C.
Schroeder, Jan-Hendrik
Rogers, Matthew E.
Raynes, John G.
author_sort Seow, Eu Shen
collection PubMed
description Human C-reactive protein (CRP) binds to lipophosphoglycan (LPG), a virulence factor of Leishmania spp., through the repeating phosphodisaccharide region. We report here that both major components of promastigote secretory gel (PSG), the filamentous proteophosphoglycan (fPPG) and the secreted acid phosphatase (ScAP), are also ligands. CRP binding was mainly associated with the flagellar pocket when LPG deficient Leishmania mexicana parasites were examined by fluorescent microscopy, consistent with binding to secreted material. ScAP is a major ligand in purified fPPG from parasite culture as demonstrated by much reduced binding to a ScAP deficient mutant fPPG in plate binding assays and ligand blotting. Nevertheless, in sandfly derived PSG fPPG is a major component and the major CRP binding component. Previously we showed high avidity of CRP for LPG ligand required multiple disaccharide repeats. ScAP and fPPG only have short repeats but they retain high avidity for CRP revealed by surface plasmon resonance because they are found in multiple copies on the phosphoglycan. The fPPG from many species such as L. donovani and L. mexicana bound CRP strongly but L. tropica and L. amazonensis had low amounts of binding. The extent of side chain substitution of [-PO(4)-6Galβ1-4Manα1-] disaccharides correlates inversely with binding of CRP. The ligand for the CRP on different species all had similar binding avidity as the half maximal binding concentration was similar. Since the PSG is injected with the parasites into host blood pools and phosphoglycans (PG) are known to deplete complement, we showed that CRP makes a significant contribution to the activation of complement by PSG using serum from naive donors.
format Online
Article
Text
id pubmed-10500826
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-105008262023-09-15 C-reactive protein binds to short phosphoglycan repeats of Leishmania secreted proteophosphoglycans and activates complement Seow, Eu Shen Doran, Eve C. Schroeder, Jan-Hendrik Rogers, Matthew E. Raynes, John G. Front Immunol Immunology Human C-reactive protein (CRP) binds to lipophosphoglycan (LPG), a virulence factor of Leishmania spp., through the repeating phosphodisaccharide region. We report here that both major components of promastigote secretory gel (PSG), the filamentous proteophosphoglycan (fPPG) and the secreted acid phosphatase (ScAP), are also ligands. CRP binding was mainly associated with the flagellar pocket when LPG deficient Leishmania mexicana parasites were examined by fluorescent microscopy, consistent with binding to secreted material. ScAP is a major ligand in purified fPPG from parasite culture as demonstrated by much reduced binding to a ScAP deficient mutant fPPG in plate binding assays and ligand blotting. Nevertheless, in sandfly derived PSG fPPG is a major component and the major CRP binding component. Previously we showed high avidity of CRP for LPG ligand required multiple disaccharide repeats. ScAP and fPPG only have short repeats but they retain high avidity for CRP revealed by surface plasmon resonance because they are found in multiple copies on the phosphoglycan. The fPPG from many species such as L. donovani and L. mexicana bound CRP strongly but L. tropica and L. amazonensis had low amounts of binding. The extent of side chain substitution of [-PO(4)-6Galβ1-4Manα1-] disaccharides correlates inversely with binding of CRP. The ligand for the CRP on different species all had similar binding avidity as the half maximal binding concentration was similar. Since the PSG is injected with the parasites into host blood pools and phosphoglycans (PG) are known to deplete complement, we showed that CRP makes a significant contribution to the activation of complement by PSG using serum from naive donors. Frontiers Media S.A. 2023-08-31 /pmc/articles/PMC10500826/ /pubmed/37720216 http://dx.doi.org/10.3389/fimmu.2023.1256205 Text en Copyright © 2023 Seow, Doran, Schroeder, Rogers and Raynes https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Seow, Eu Shen
Doran, Eve C.
Schroeder, Jan-Hendrik
Rogers, Matthew E.
Raynes, John G.
C-reactive protein binds to short phosphoglycan repeats of Leishmania secreted proteophosphoglycans and activates complement
title C-reactive protein binds to short phosphoglycan repeats of Leishmania secreted proteophosphoglycans and activates complement
title_full C-reactive protein binds to short phosphoglycan repeats of Leishmania secreted proteophosphoglycans and activates complement
title_fullStr C-reactive protein binds to short phosphoglycan repeats of Leishmania secreted proteophosphoglycans and activates complement
title_full_unstemmed C-reactive protein binds to short phosphoglycan repeats of Leishmania secreted proteophosphoglycans and activates complement
title_short C-reactive protein binds to short phosphoglycan repeats of Leishmania secreted proteophosphoglycans and activates complement
title_sort c-reactive protein binds to short phosphoglycan repeats of leishmania secreted proteophosphoglycans and activates complement
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10500826/
https://www.ncbi.nlm.nih.gov/pubmed/37720216
http://dx.doi.org/10.3389/fimmu.2023.1256205
work_keys_str_mv AT seoweushen creactiveproteinbindstoshortphosphoglycanrepeatsofleishmaniasecretedproteophosphoglycansandactivatescomplement
AT doranevec creactiveproteinbindstoshortphosphoglycanrepeatsofleishmaniasecretedproteophosphoglycansandactivatescomplement
AT schroederjanhendrik creactiveproteinbindstoshortphosphoglycanrepeatsofleishmaniasecretedproteophosphoglycansandactivatescomplement
AT rogersmatthewe creactiveproteinbindstoshortphosphoglycanrepeatsofleishmaniasecretedproteophosphoglycansandactivatescomplement
AT raynesjohng creactiveproteinbindstoshortphosphoglycanrepeatsofleishmaniasecretedproteophosphoglycansandactivatescomplement