Removal of natural anti-αGal antibodies elicits protective immunity against Gram-negative bacterial infections

Antibody-dependent enhancement (ADE) of bacterial infections occurs when blocking or inhibitory antibodies facilitate the infectivity of pathogens. In humans, antibodies involved in ADE of bacterial infections may include those naturally produced against Gal alpha 1-3Gal beta 1-4GlcNAc beta (alpha G...

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Autores: Olivera Ardid, Sara, Bello Gil, Daniel, Pérez Cruz, Magdiel, Costa, Cristina, Camoez, Mariana, Domínguez Luzón, Ma. Ángeles (María Ángeles), Ferrero Alves, Yara, Vaquero, Jose Miguel, Khasbiullina, Nailya, Shilova, Nadezhda V., Bovin, Nicolai V., Mañez, Rafael
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/203062
Acceso en línea:https://hdl.handle.net/2445/203062
Access Level:acceso abierto
Palabra clave:Immunoglobulina G
Bacteriologia
Immunoglobulin G
Bacteriology
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spelling Removal of natural anti-αGal antibodies elicits protective immunity against Gram-negative bacterial infectionsOlivera Ardid, SaraBello Gil, DanielPérez Cruz, MagdielCosta, CristinaCamoez, MarianaDomínguez Luzón, Ma. Ángeles (María Ángeles)Ferrero Alves, YaraVaquero, Jose MiguelKhasbiullina, NailyaShilova, Nadezhda V.Bovin, Nicolai V.Mañez, RafaelImmunoglobulina GBacteriologiaImmunoglobulin GBacteriologyAntibody-dependent enhancement (ADE) of bacterial infections occurs when blocking or inhibitory antibodies facilitate the infectivity of pathogens. In humans, antibodies involved in ADE of bacterial infections may include those naturally produced against Gal alpha 1-3Gal beta 1-4GlcNAc beta (alpha Gal). Here, we investigate whether eliminating circulating anti-alpha Gal antibodies using a soluble alpha Gal glycopolymer confers protection against Gram-negative bacterial infections. We demonstrated that the in vivo intra-corporeal removal of anti-alpha Gal antibodies in alpha 1,3-galactosyltransferase knockout (GalT-KO) mice was associated with protection against mortality from Gram-negative sepsis after cecal ligation and puncture (CLP). The improved survival of GalT-KO mice was associated with an increased killing capacity of serum against Escherichia coli isolated after CLP and reduced binding of IgG1 and IgG3 to the bacteria. Additionally, inhibition of anti-alpha Gal antibodies from human serum in vitro increases the bactericidal killing of E. coli O86:B7 and multidrug-resistant Klebsiella pneumoniae and Pseudomonas aeruginosa. In the case of E. coli O86:B7, there was also an improvement in bacteria opsonophagocytosis by macrophages. Both lytic mechanisms were related to a decreased binding of IgG2 to the bacteria. Our results show that protective immunity against Gram-negative bacterial pathogens can be elicited, and infectious diseases caused by these bacteria can be prevented by removing natural anti-alpha Gal antibodies.Frontiers Media SA2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/203062Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3389/fimmu.2023.1232924Frontiers in Immunology, 2023, vol. 14https://doi.org/10.3389/fimmu.2023.1232924cc by (c) Olivera Ardid, Sara et al., 2023http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2030622026-05-27T06:46:51Z
dc.title.none.fl_str_mv Removal of natural anti-αGal antibodies elicits protective immunity against Gram-negative bacterial infections
title Removal of natural anti-αGal antibodies elicits protective immunity against Gram-negative bacterial infections
spellingShingle Removal of natural anti-αGal antibodies elicits protective immunity against Gram-negative bacterial infections
Olivera Ardid, Sara
Immunoglobulina G
Bacteriologia
Immunoglobulin G
Bacteriology
title_short Removal of natural anti-αGal antibodies elicits protective immunity against Gram-negative bacterial infections
title_full Removal of natural anti-αGal antibodies elicits protective immunity against Gram-negative bacterial infections
title_fullStr Removal of natural anti-αGal antibodies elicits protective immunity against Gram-negative bacterial infections
title_full_unstemmed Removal of natural anti-αGal antibodies elicits protective immunity against Gram-negative bacterial infections
title_sort Removal of natural anti-αGal antibodies elicits protective immunity against Gram-negative bacterial infections
dc.creator.none.fl_str_mv Olivera Ardid, Sara
Bello Gil, Daniel
Pérez Cruz, Magdiel
Costa, Cristina
Camoez, Mariana
Domínguez Luzón, Ma. Ángeles (María Ángeles)
Ferrero Alves, Yara
Vaquero, Jose Miguel
Khasbiullina, Nailya
Shilova, Nadezhda V.
Bovin, Nicolai V.
Mañez, Rafael
author Olivera Ardid, Sara
author_facet Olivera Ardid, Sara
Bello Gil, Daniel
Pérez Cruz, Magdiel
Costa, Cristina
Camoez, Mariana
Domínguez Luzón, Ma. Ángeles (María Ángeles)
Ferrero Alves, Yara
Vaquero, Jose Miguel
Khasbiullina, Nailya
Shilova, Nadezhda V.
Bovin, Nicolai V.
Mañez, Rafael
author_role author
author2 Bello Gil, Daniel
Pérez Cruz, Magdiel
Costa, Cristina
Camoez, Mariana
Domínguez Luzón, Ma. Ángeles (María Ángeles)
Ferrero Alves, Yara
Vaquero, Jose Miguel
Khasbiullina, Nailya
Shilova, Nadezhda V.
Bovin, Nicolai V.
Mañez, Rafael
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Immunoglobulina G
Bacteriologia
Immunoglobulin G
Bacteriology
topic Immunoglobulina G
Bacteriologia
Immunoglobulin G
Bacteriology
description Antibody-dependent enhancement (ADE) of bacterial infections occurs when blocking or inhibitory antibodies facilitate the infectivity of pathogens. In humans, antibodies involved in ADE of bacterial infections may include those naturally produced against Gal alpha 1-3Gal beta 1-4GlcNAc beta (alpha Gal). Here, we investigate whether eliminating circulating anti-alpha Gal antibodies using a soluble alpha Gal glycopolymer confers protection against Gram-negative bacterial infections. We demonstrated that the in vivo intra-corporeal removal of anti-alpha Gal antibodies in alpha 1,3-galactosyltransferase knockout (GalT-KO) mice was associated with protection against mortality from Gram-negative sepsis after cecal ligation and puncture (CLP). The improved survival of GalT-KO mice was associated with an increased killing capacity of serum against Escherichia coli isolated after CLP and reduced binding of IgG1 and IgG3 to the bacteria. Additionally, inhibition of anti-alpha Gal antibodies from human serum in vitro increases the bactericidal killing of E. coli O86:B7 and multidrug-resistant Klebsiella pneumoniae and Pseudomonas aeruginosa. In the case of E. coli O86:B7, there was also an improvement in bacteria opsonophagocytosis by macrophages. Both lytic mechanisms were related to a decreased binding of IgG2 to the bacteria. Our results show that protective immunity against Gram-negative bacterial pathogens can be elicited, and infectious diseases caused by these bacteria can be prevented by removing natural anti-alpha Gal antibodies.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/203062
url https://hdl.handle.net/2445/203062
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2023.1232924
Frontiers in Immunology, 2023, vol. 14
https://doi.org/10.3389/fimmu.2023.1232924
dc.rights.none.fl_str_mv cc by (c) Olivera Ardid, Sara et al., 2023
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Olivera Ardid, Sara et al., 2023
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media SA
publisher.none.fl_str_mv Frontiers Media SA
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300724

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