Neutrophils negatively regulate induction of mucosal IgA responses after sublingual immunization

• Published in: Mucosal immunology Vol. 8; no. 4; pp. 735 - 745
• Main Authors: Jee, J, Bonnegarde-Bernard, A, Duverger, A, Iwakura, Y, Cormet-Boyaka, E, Martin, T L, Steiner, H E, Bachman, R C, Boyaka, P N
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-07-2015; Elsevier Limited
• Subjects: 631/250/24/590/2291; 631/250/2504/223/1699; 631/250/251/1567; 631/250/347; Administration, Sublingual; Allergology; Animals; Antibodies; Antibody Formation; Antigens, Bacterial - immunology; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Bacterial Toxins - immunology; Biomedical and Life Sciences; Biomedicine; Gastroenterology; I-kappa B Kinase - deficiency; I-kappa B Kinase - metabolism; Immunity, Mucosal; Immunization; Immunoglobulin A, Secretory - immunology; Immunology; Leukocyte Count; Lymph Nodes - immunology; Mice; Mice, Transgenic; Mucous Membrane - immunology; Mucous Membrane - metabolism; Myeloid Cells - immunology; Myeloid Cells - metabolism; Neutrophil Infiltration - immunology; Neutrophils - immunology; Neutrophils - metabolism; Signal Transduction
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/mi.2014.105

Induction of mucosal immunoglobulin-A (IgA) capable of providing a first line of defense against bacterial and viral pathogens remains a major goal of needle-free vaccines given via mucosal routes. Innate immune cells are known to play a central role in induction of IgA responses by mucosal vaccines, but the relative contribution of myeloid cell subsets to these responses has not firmly been established. Using an
in vivo
model of sublingual vaccination with
Bacillus anthracis
edema toxin (EdTx) as adjuvant, we examined the role of myeloid cell subsets for mucosal secretory IgA responses. Sublingual immunization of wild-type mice resulted in a transient increase of neutrophils in sublingual tissues and cervical lymph nodes. These mice later developed Ag-specific serum IgG responses, but not serum or mucosal IgA. Interestingly, EdTx failed to increase neutrophils in sublingual tissues and cervical lymph nodes of IKKβ
ΔMye
mice, and these mice developed IgA responses. Partial depletion of neutrophils before immunization of wild-type mice allowed the development of both mucosal and serum IgA responses. Finally, co-culture of B cells with neutrophils from either wild-type or IKKβ
ΔMye
mice suppressed secretion of IgA, but not IgM or IgG. These results identify a new role for neutrophils as negative regulators of IgA responses.