Human Immature Dendritic Cells Efficiently Bind and Take up Secretory IgA Without the Induction of Maturation

Abstract

Immature dendritic cells (DC) reside in peripheral tissues, where they pick up and process incoming pathogens via scavenger receptors or FcR such as FcγR and FcεR. At mucosal surfaces, IgA is the main Ig to protect the body from incoming pathogens. In addition, DC are present in high numbers at these sites. We detected expression of FcαR (CD89) on the CD14+ population of CD34+ progenitor-derived DC and on monocyte-derived DC (MoDC). However, CD89 expression was strongly decreased upon differentiation from monocyte to DC. We found only minimal binding of serum IgA to MoDC but strong binding of secretory IgA (SIgA). The SIgA binding to MoDC could not be blocked by anti-CD89 blocking Abs. DC efficiently internalized SIgA, but not serum IgA, and uptake of SIgA could be blocked by specific sugars or partially by Ab reactive with mannose receptor. Importantly, binding and uptake of SIgA was not accompanied by signs of DC maturation, such as increased expression of CD86 and CD83 or induction of cytokine secretion. These data indicate that SIgA can interact with DC not via CD89, but via carbohydrate-recognizing receptors like mannose receptor and suggest that uptake of SIgA-containing immune complexes by immature DC may be a mechanism to modulate mucosal immune responses.

Roundtrip Ticket for Secretory IgA: Role in Mucosal Homeostasis?

“…An additional property of IgA is its inability to trigger the release of inflammatory mediators through receptors specific for its Fc domain (42)(43)(44). In support of this are two reports showing differential pattern of in vitro-derived DC activation after surface binding of IgA as compared with other Ig isotypes (45,46). This is consistent with the multitask role of protecting against foreign substances and microbes, regulating the commensal microbiota, while at the same time not subjecting the mucosa to undue inflammation (47,48).…”

Grass Pollen Immunotherapy Induces an Allergen-Specific IgA2 Antibody Response Associated with Mucosal TGF-β Expression

“…The source of IL-10 following IT consists of T cells and, later on, monocytic cells (27,39,42). The induction of IL-10 in monocytes/macrophages by IgG has previously been reported (44); Geissman et al (45) reported on IL-10 responses to IgA in dendritic cells while Heystek et al (46) did not observe any cytokine response of these monocyte-derived cells expressing low levels of Fc␣RI. In our study, freshly purified peripheral monocytes stimulated by IgA also secreted IL-10, the robust response to p-IgA2 fractions relating probably to higher IgA Ab levels, as no significant difference in IL-10 release was observed between (purified) IgA subclasses.…”

Human NK cells express Fc receptors for IgA which mediate signal transduction and target cell killing

“…The MR is a marker of alternatively activated cells with enhanced cell function, mediates both pinocytosis and phagocytosis, and serves as a molecular link between innate and adaptive immune response [26]. Because DC efficiently bind sIgA [7] via a receptor with lectin-like properties [25], we were interested to know whether NK cells may bind sIgA via MR. NK cells and monocytes did not bind anti-MR Ab, whereas the MR is highly expressed on monocyte-derived DC [29], as well as on monocyte-derived M ¶ [4]. Furthermore, the percentage of NK (CD3 -CD56 + ) cells binding sIgA did not change when L-fucose, D-galactose, D-glucose, D-mannose or N-acetyl-D-glucosamine were used as inhibitors.…”

“…It has recently been shown that DC express a receptor for IgA [7], and that the binding of IgA occurs via a mannose receptor (MR/CD206) which recognizes carbohydrates patterns [25]. Therefore, we asked whether NK cells constitutively express MR, which may mediate sIgA binding.…”