Gut Microbiota Abrogates Anti-α-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-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.

The antibody response to the glycan α‐Gal correlates with COVID‐19 disease symptoms

“…Finally, the higher representation of antiα-Gal IgA antibodies in ICU patients may be associated with the inflammatory response observed in these cases. In accordance with these results, it was recently shown in endogenous α-Gal-negative turkeys that treatment with probiotic bacteria with high α-Gal content results in protection against aspergillosis through reduction by still unknown mechanisms in the proinflammatory anti-α-Gal IgA response in the lungs [27]. Based on the fact that natural antibodies against α-Gal are produced in response to bacteria with this modification in the microbiota [10], our hypothesis is that the dysbacteriosis observed in COVID-19 patients [28] translates into a reduction in total anti-α-Gal antibody titers and alteration of anti-α-Gal antibody isotype composition due to the reduction in the microbiota of α-Gal-containing commensal bacteria and other still uncharacterized mechanisms ( Figure 5).…”

“…Finally, the higher representation of anti‐α‐Gal IgA antibodies in ICU patients may be associated with the inflammatory response observed in these cases. In accordance with these results, it was recently shown in endogenous α‐Gal‐negative turkeys that treatment with probiotic bacteria with high α‐Gal content results in protection against aspergillosis through reduction by still unknown mechanisms in the pro‐inflammatory anti‐α‐Gal IgA response in the lungs 29 …”

Anti-Tick Microbiota Vaccine Impacts Ixodes ricinus Performance during Feeding

“…The synthesis of the glycan Galα1-3Galβ1-4GlcNAc-R (α-Gal) by the enzyme α-1,3-galactosyltransferase occurs in bacteria [ 10 , 11 , 12 , 13 ], fungi [ 14 , 15 , 16 ], and noncatarrhine mammals [ 17 ], but prokaryotic and eukaryotic α-1,3-galactosyltransferase genes and proteins share little structural homology [ 18 , 19 , 20 ]. Humans, old world monkeys and apes evolved with the inability to synthesize α-Gal, which resulted in the capacity to produce anti-α-Gal IgM/IgG antibodies with a protective activity against pathogenic viruses (e.g., HIV), bacteria (e.g., Mycobacterium ) and parasites (e.g., Plasmodium ), containing this modification on membrane proteins [ 21 , 22 , 23 ].…”

Aspergillosis in Wild Birds

“…Vaccination strategies have been attempted in birds but with inconsistent results [ 115 , 126 , 249 , 250 ].…”