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Gut Microbiota Abrogates Anti-?-Gal IgA Response in Lungs and Protects against Experimental Aspergillus Infection in Poultry.

ABSTRACT: Naturally occurring human antibodies (Abs) of the isotypes IgM and IgG and reactive to the galactose-?-1,3-galactose (?-Gal) epitope are associated with protection against infectious diseases, caused by pathogens expressing the glycan. Gut microbiota bacteria expressing ?-Gal regulate the immune response to this glycan in animals lacking endogenous ?-Gal. Here, we asked whether the production of anti-?-Gal Abs in response to microbiota stimulation in birds, confers protection against infection by Aspergillus fumigatus, a major fungal pathogen that expresses ?-Gal in its surface. We demonstrated that the oral administration of Escherichia coli O86:B7 strain, a bacterium with high ?-Gal content, reduces the occurrence of granulomas in lungs and protects turkeys from developing acute aspergillosis. Surprisingly, the protective effect of E. coli O86:B7 was not associated with an increase in circulating anti-?-Gal IgY levels, but with a striking reduction of anti-?-Gal IgA in the lungs of infected turkeys. Subcutaneous immunization against ?-Gal did not induce a significant reduction of lung anti-?-Gal IgA and failed to protect against an infectious challenge with A. fumigatus. Oral administration of E. coli O86:B7 was not associated with the upregulation of lung cytokines upon A. fumigatus infection. We concluded that the oral administration of bacteria expressing high levels of ?-Gal decreases the levels of lung anti-?-Gal IgA, which are mediators of inflammation and lung damage during acute aspergillosis.

PROVIDER: S-EPMC7350254 | BioStudies |

REPOSITORIES: biostudies

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Project description:The protozoan parasite, Trypanosoma cruzi, the etiologic agent of Chagas disease (ChD), has a cell surface covered by immunogenic glycoconjugates. One of the immunodominant glycotopes, the trisaccharide Gal?(1,3)Gal?(1,4)GlcNAc?, is expressed on glycosylphosphatidylinositol-anchored mucins of the infective trypomastigote stage of T. cruzi and triggers high levels of protective anti-?-Gal antibodies (Abs) in infected individuals. Here, we have efficiently synthesized the mercaptopropyl glycoside of that glycotope and conjugated it to maleimide-derivatized bovine serum albumin (BSA). Chemiluminescent-enzyme-linked immunosorbent assay revealed that Gal?(1,3)Gal?(1,4)GlcNAc?-BSA is recognized by purified anti-?-Gal Abs from chronic ChD patients ?230-fold more strongly than by anti-?-Gal Abs from sera of healthy individuals (NHS anti-?-Gal). Similarly, the pooled sera of chronic Chagas disease patients (ChHSP) recognized Gal?(1,3)Gal?(1,4)GlcNAc? ?20-fold more strongly than pooled NHS. In contrast, the underlying disaccharide Gal?(1,4)GlcNAc? and the monosaccharide GlcNAc? or GlcNAc? conjugated to BSA are poorly or not recognized by purified anti-?-Gal Abs or sera from Chagasic patients or healthy individuals. Our results highlight the importance of the terminal Gal? moiety for recognition by Ch anti-?-Gal Abs and the lack of Abs against nonself Gal?(1,4)GlcNAc? and GlcNAc? glycotopes. The substantial difference in binding of Ch vs. NHS anti-?-Gal Abs to Gal?(1,3)Gal?(1,4)GlcNAc?-BSA suggests that this neoglycoprotein (NGP) might be suitable for experimental vaccination. To this end, the Gal?(1,3)Gal?(1,4)GlcNAc?-BSA NGP was then used to immunize ?1,3-galactosyltransferase-knockout mice, which produced antibody titers 40-fold higher as compared with pre-immunization titers. Taken together, our results indicate that the synthetic Gal?(1,3)Gal?(1,4)GlcNAc? glycotope coupled to a carrier protein could be a potential diagnostic and vaccine candidate for ChD.

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Gut Microbiota Abrogates Anti-?-Gal IgA Response in Lungs and Protects against Experimental Aspergillus Infection in Poultry.

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