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http://hdl.handle.net/2445/203062
Title: | Removal of natural anti-αGal antibodies elicits protective immunity against Gram-negative bacterial infections |
Author: | Olivera Ardid, Sara Bello Gil, Daniel Pérez Cruz, Magdiel Costa, Cristina Camoez, Mariana Dominguez, M. Angeles Ferrero Alves, Yara Vaquero, Jose Miguel Khasbiullina, Nailya Shilova, Nadezhda V. Bovin, Nicolai V. Mañez, Rafael |
Keywords: | Immunoglobulina G Bacteriologia Immunoglobulin G Bacteriology |
Issue Date: | 18-Aug-2023 |
Publisher: | Frontiers Media SA |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2023.1232924 |
It is part of: | Frontiers in Immunology, 2023, vol. 14 |
URI: | http://hdl.handle.net/2445/203062 |
Related resource: | https://doi.org/10.3389/fimmu.2023.1232924 |
ISSN: | 1664-3224 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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fimmu-14-1232924.pdf | 9.44 MB | Adobe PDF | View/Open |
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