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

Autor:in

Hernández, Lourdes; Castillo, Veronica; Villa, Edgar; Humaran, Luis; Alberdi, Pilar; Hodzic, Adnan; Hernandez-Jarguin, Angelica; RAKOTOBE, Sabine; Galon, Clemence; Devillers, Elodie; de la Fuente, José; Guillot, Jacques; Cabezas-Cruz, Alejandro

Abstrakt

Naturally occurring human antibodies (Abs) of the isotypes IgM and IgG and reactive to the galactose-alpha-1,3-galactose (alpha-Gal) epitope are associated with protection against infectious diseases, caused by pathogens expressing the glycan. Gut microbiota bacteria expressing alpha-Gal regulate the immune response to this glycan in animals lacking endogenous alpha-Gal. Here, we asked whether the production of anti-alpha-Gal Abs in response to microbiota stimulation in birds, confers protection against infection by Aspergillus fumigatus, a major fungal pathogen that expresses alpha-Gal in its surface. We demonstrated that the oral administration of Escherichia coli O86:B7 strain, a bacterium with high alpha-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-alpha-Gal IgY levels, but with a striking reduction of anti-alpha-Gal IgA in the lungs of infected turkeys. Subcutaneous immunization against alpha-Gal did not induce a significant reduction of lung anti-alpha-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 alpha-Gal decreases the levels of lung anti-alpha-Gal IgA, which are mediators of inflammation and lung damage during acute aspergillosis.

Dokumententyp

Originalarbeit

Open Access Type

Gold

WoS ID

WOS:000550827600001