Abstract
Naturally occurring human antibodies (Abs) of the isotypes IgM and IgG and reactive to the galactose-α-1,3-galactose (α-Gal) epitope are associated with protection against infectious diseases, caused by pathogens expressing the glycan. Gut microbiota bacteria expressing α-Gal regulate the immune response to this glycan in animals lacking endogenous α-Gal. Here, we asked whether the production of anti-α-Gal Abs in response to microbiota stimulation in birds, confers protection against infection by Aspergillus fumigatus, a major fungal pathogen that expresses α-Gal in its surface. We demonstrated that the oral administration of Escherichia coli O86:B7 strain, a bacterium with high α-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-α-Gal IgY levels, but with a striking reduction of anti-α-Gal IgA in the lungs of infected turkeys. Subcutaneous immunization against α-Gal did not induce a significant reduction of lung anti-α-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 α-Gal decreases the levels of lung anti-α-Gal IgA, which are mediators of inflammation and lung damage during acute aspergillosis.
Highlights
Galactose-α-1,3-galactose (α-Gal) is an oligosaccharide abundantly expressed on the glycoproteins and glycolipids of non-primate mammals, prosimians, and New World monkeys and is synthesized by the enzyme α-1,3-galactosyltransferase, encoded by the gene ggta1 [1]
The association of α-Gal to fungal proteins was assessed by an inhibition ELISA in which the reactivity of mAb M86 was measured following a pre-incubation with proteins extracted from Ascomycota species, including A. fumigatus, Aspergillus nidulans, Candida glabrata, Candida albicans, Microsporum canis, Penicillium sp., Scedosporium sp., and Trichophyton benhamiae and the Zygomycota fungi Mucor sp. and Rhizopus sp
We showed that gut microbiota bacteria expressing high levels of α-Gal protect turkeys against aspergillosis
Summary
Galactose-α-1,3-galactose (α-Gal) is an oligosaccharide abundantly expressed on the glycoproteins and glycolipids of non-primate mammals, prosimians, and New World monkeys and is synthesized by the enzyme α-1,3-galactosyltransferase, encoded by the gene ggta1 [1]. Based on the protective role of anti-α-Gal Abs, it was suggested that the inactivation of ggta was due to strong selective pressure exerted on primate ancestors by an infectious agent, expressing α-Gal [3]. In support to this hypothesis, gut colonization by E. coli O86:B7 elicits anti-α-Gal IgM that protected α-Gal-deficient mouse against malaria transmission by Anopheles mosquitoes [8]. High levels of anti-α-Gal IgG and IgM in humans were associated with protection to Plasmodium sp., a pathogen expressing the antigen α-Gal, in malaria endemic regions [7,8]. The α-Gal immunity evolved as a trade-off between the protection to pathogens expressing α-Gal, which is mediated by anti-α-Gal
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