SIgA–Shigella Immune Complexes Interact with Dectin-1 and SIGNR3 to Differentially Regulate Mouse Peyer's Patch and Mesenteric Lymph Node Dendritic Cell's Responsiveness. Issue 15 (21st July 2017)

• Record Type: Journal Article
• Authors: Mikulic, Josip; Bioley, Gilles; Corthésy, Blaise
• Is Part Of: Journal of molecular biology. Volume 429:Issue 15(2017)
• Page Start: 2387
• Page End: 2400
• Publication Date: 2017-07-21
• Subjects: SIgA secretory IgA -- M cells microfold cells -- PP Peyer's patch -- DC dendritic cell -- MLN mesenteric lymph node -- SIGNR1 specific intercellular adhesion molecule-3 grabbing non-integrin receptor 1 -- SIGNR3 specific intercellular adhesion molecule-3 grabbing non-integrin receptor 3 -- Sf Shigella flexneri -- KC keratinocyte-derived cytokine -- pIgA polymeric IgA -- CLR C-type lectin receptor -- IC immune complex -- FCS fetal calf serum -- CFSE carboxyfluorescein succinimidyl ester -- LPS lipopolysaccharide -- PBS phosphate-buffered saline; secretory IgA -- dendritic cells -- Dectin-1 -- SIGNR3 -- cytokines; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2017.05.024
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: In addition to contributing to immune exclusion at mucosal surfaces, secretory IgA (SIgA) made of polymeric IgA and secretory component is able to selectively reenter via microfold cells into Peyer's patches (PPs) present along the intestine and to associate with dendritic cells (DCs) of the CD11c + CD11b + MHCII + F4/80 − CD8 − phenotype in the subepithelial dome region and the draining mesenteric lymph nodes (MLNs). However, the nature of the receptor(s) for SIgA on murine PP and MLN DCs is unknown. We find that glycosylated secretory component moiety and polymeric IgA are both involved in the specific interaction with these cells. Using blocking antibodies and competition experiments, we identify Dectin-1 and specific intercellular adhesion molecule-3 grabbing non-integrin receptor 3 (SIGNR3) as receptors for SIgA. While SIgA-commensal immune complexes (ICs) contribute to local homeostasis upon interaction with mucosal DCs, the picture is less clear for pathogenic agents. We find that in comparison with incubation of Shigella flexneri alone, association of the enteropathogen with SIgA prompts freshly isolated DCs from PPs and MLNs to invert the production of pro- versus non-inflammatory cytokines/chemokines. The sum of the data suggests that in contrast to IgG-based ICs boosting immune reactivity of antigen-presenting cells, SIgA produced during an ongoing immune response can, in addition to its known function of immune exclusion, modulate mucosal DC conditioning via specific interaction with Dectin-1 and SIGNR3. Graphical Abstract: Highlights: In the gut, SIgA acts as a non-inflammatory antibody via poorly defined mechanisms. SIgA is recruited by Dectin-1 and SIGNR3 on PP and MLN DC. SIgA– S. flexneri ICs modulate PP and MLN DC responsiveness. SIgA-based ICs dampen DC inflammatory response via Dectin-1 and promotes TGF-β via SIGNR3. During ongoing immune responses, SIgA-based ICs favor return to homeostasis.