title: IL-17A Is an Important Effector of the Immune Response of the Mammary Gland to Escherichia coli Infection.
abstract: The cytokine IL-17A has been shown to play critical roles in host defense against bacterial and fungal infections at different epithelial sites, but its role in the defense of the mammary gland (MG) has seldom been investigated, although infections of the MG constitute the main pathology afflicting dairy cows. In this study, we showed that IL-17A contributes to the defense of the MG against Escherichia coli infection by using a mouse mastitis model. After inoculation of the MG with a mastitis-causing E. coli strain, the bacterial load increased rapidly, triggering an intense influx of leukocytes into mammary tissue and increased concentrations of IL-6, IL-22, TNF-α, and IL-10. Neutrophils were the first cells that migrated intensely to the mammary tissue, in line with an early production of CXCL2. Depletion of neutrophils induced an increased mammary bacterial load. There was a significant increase of IL-17-containing CD4(+) αβ T lymphocyte numbers in infected glands. Depletion of IL-17A correlated with an increased bacterial colonization and IL-10 production. Intramammary infusion of IL-17A at the onset of infection was associated with markedly decreased bacterial numbers, decreased IL-10 production, and increased neutrophil recruitment. Depletion of CD25(+) regulatory T cells correlated with a decreased production of IL-10 and a reduced bacterial load. These results indicate that IL-17A is an important effector of MG immunity to E. coli and suggest that an early increased local production of IL-17A would improve the outcome of infection. These findings point to a new lead to the development of vaccines against mastitis.
authors.affiliation: UMR1282 Infectiologie et Santé Publique, Institut National de la Recherche Agronomique, F-37380 Nouzilly, France; and UMR1282 Infectiologie et Santé Publique, Université François-Rabelais de Tours, F-37000 Tours, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Porcherie
authors.affiliation: UMR1282 Infectiologie et Santé Publique, Institut National de la Recherche Agronomique, F-37380 Nouzilly, France; and UMR1282 Infectiologie et Santé Publique, Université François-Rabelais de Tours, F-37000 Tours, France.
authors.forename: Florence B
authors.initials: FB
authors.lastname: Gilbert
authors.affiliation: UMR1282 Infectiologie et Santé Publique, Institut National de la Recherche Agronomique, F-37380 Nouzilly, France; and UMR1282 Infectiologie et Santé Publique, Université François-Rabelais de Tours, F-37000 Tours, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Germon
authors.affiliation: UMR1282 Infectiologie et Santé Publique, Institut National de la Recherche Agronomique, F-37380 Nouzilly, France; and UMR1282 Infectiologie et Santé Publique, Université François-Rabelais de Tours, F-37000 Tours, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Cunha
authors.affiliation: UMR1282 Infectiologie et Santé Publique, Institut National de la Recherche Agronomique, F-37380 Nouzilly, France; and UMR1282 Infectiologie et Santé Publique, Université François-Rabelais de Tours, F-37000 Tours, France.
authors.forename: Angélina
authors.identifier: http://orcid.org/0000-0003-1295-3821
authors.initials: A
authors.lastname: Trotereau
authors.affiliation: UMR1282 Infectiologie et Santé Publique, Institut National de la Recherche Agronomique, F-37380 Nouzilly, France; and UMR1282 Infectiologie et Santé Publique, Université François-Rabelais de Tours, F-37000 Tours, France.
authors.forename: Christelle
authors.identifier: http://orcid.org/0000-0003-3211-4304
authors.initials: C
authors.lastname: Rossignol
authors.affiliation: UMR1282 Infectiologie et Santé Publique, Institut National de la Recherche Agronomique, F-37380 Nouzilly, France; and UMR1282 Infectiologie et Santé Publique, Université François-Rabelais de Tours, F-37000 Tours, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Winter
authors.affiliation: UMR1282 Infectiologie et Santé Publique, Institut National de la Recherche Agronomique, F-37380 Nouzilly, France; and UMR1282 Infectiologie et Santé Publique, Université François-Rabelais de Tours, F-37000 Tours, France.
authors.forename: Patricia
authors.identifier: http://orcid.org/0000-0002-3491-7613
authors.initials: P
authors.lastname: Berthon
authors.affiliation: UMR1282 Infectiologie et Santé Publique, Institut National de la Recherche Agronomique, F-37380 Nouzilly, France; and UMR1282 Infectiologie et Santé Publique, Université François-Rabelais de Tours, F-37000 Tours, France pascal.rainard@tours.inra.fr.
authors.forename: Pascal
authors.identifier: http://orcid.org/0000-0002-5477-2626
authors.initials: P
authors.lastname: Rainard
mesh_terms: D000818:Animals; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000276:immunology*; D008321:Mammary Glands, Animal / Q000276:immunology; D008413:Mastitis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D016207:Cytokines; D020381:Interleukin-17