Secretory IgA Possesses Intrinsic Modulatory Properties Stimulating Mucosal and Systemic Immune Responses

Favre, Laurent; Spertini, François; Corthésy, Blaise

doi:10.4049/jimmunol.175.5.2793

Cited by 99 publications

(67 citation statements)

References 58 publications

(51 reference statements)

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“…We postulate that such a monitoring mechanism would promote optimal gut microbial colonization and ensures a dynamic and plastic interplay with epithelial cells. This adds to the already documented role of SIgA in limiting dissemination of microorganisms in the gastrointestinal lymphoid tissue (17,34), and the immunomodulatory properties of SIgA in the intestine (35)(36)(37). Together, this will result in the onset of modulatory pathways crucial to maturation of both the epithelium and innate and adaptive immunity.…”

Section: Discussionmentioning

confidence: 98%

Potentiation of Polarized Intestinal Caco-2 Cell Responsiveness to Probiotics Complexed with Secretory IgA

Mathias

Duc

Favre

et al. 2010

Journal of Biological Chemistry

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The precise mechanisms underlying the interaction between intestinal bacteria and the host epithelium lead to multiple consequences that remain poorly understood at the molecular level. Deciphering such events can provide valuable information as to the mode of action of commensal and probiotic microorganisms in the gastrointestinal environment. Potential roles of such microorganisms along the privileged target represented by the mucosal immune system include maturation prior, during and after weaning, and the reduction of inflammatory reactions in pathogenic conditions. Using human intestinal epithelial Caco-2 cell grown as polarized monolayers, we found that association of a Lactobacillus or a Bifidobacterium with nonspecific secretory IgA (SIgA) enhanced probiotic adhesion by a factor of 3.4-fold or more. Bacteria alone or in complex with SIgA reinforced transepithelial electrical resistance, a phenomenon coupled with increased phosphorylation of tight junction proteins zonula occludens-1 and occludin. In contrast, association with SIgA resulted in both enhanced level of nuclear translocation of NF-B and production of epithelial polymeric Ig receptor as compared with bacteria alone. Moreover, thymic stromal lymphopoietin production was increased upon exposure to bacteria and further enhanced with SIgA-based complexes, whereas the level of pro-inflammatory epithelial cell mediators remained unaffected. Interestingly, SIgA-mediated potentiation of the Caco-2 cell responsiveness to the two probiotics tested involved Fab-independent interaction with the bacteria. These findings add to the multiple functions of SIgA and underscore a novel role of the antibody in interaction with intestinal bacteria.

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Section: Discussionmentioning

confidence: 98%

Potentiation of Polarized Intestinal Caco-2 Cell Responsiveness to Probiotics Complexed with Secretory IgA

Mathias

Duc

Favre

et al. 2010

Journal of Biological Chemistry

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“…Such an issue was tackled following oral immunization of naive mice with engineered SIgA molecules consisting of mouse pIgA and human SC serving as a non-selfAg. The recombinant Ab induced mucosal and systemic responses against human SC in the absence of any mucosal adjuvant (59). Engineered SIgA triggered production of human SCspecific Abs, human SC-dependent mixed Th1/Th2 type of responses, preserved or induced IL-10 and TGF-␤ expression in MLN, and migration and maturation of DC along the Peyer's patch-MLN-spleen axis.…”

Section: Modulation Of Immune Responses By Sigamentioning

confidence: 99%

Roundtrip Ticket for Secretory IgA: Role in Mucosal Homeostasis?

Corthésy¹

2007

The Journal of Immunology

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193

148

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An important activity of mucosal surfaces is the production of Ab referred to as secretory IgA (SIgA). SIgA serves as the first line of defense against microorganisms through a mechanism called immune exclusion. In addition, SIgA adheres selectively to M cells in intestinal Peyer’s patches, thus mediating the transepithelial transport of the Ab molecule from the intestinal lumen to underlying gut-associated organized lymphoid tissue. In Peyer’s patches, SIgA binds and is internalized by dendritic cells in the subepithelial dome region. When used as carrier for Ags in oral immunization, SIgA induces mucosal and systemic responses associated with production of anti-inflammatory cytokines and limits activation of dendritic cells. In terms of humoral immunity at mucosal surfaces, SIgA appears thus to combine properties of a neutralizing agent (immune exclusion) and of a mucosal immunopotentiator inducing effector immune responses in a noninflammatory context favorable to preserve local homeostasis of the gastrointestinal tract.

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“…Uptake of SIgA by PPs targeted this class of Ab to dendritic cells (DCs) in the subepithelial dome (SED) region and T cells in the interfollicular regions (IFRs), and this had raised the question of the immunological consequences of such an interaction in modulating ongoing mucosal immune responses and/or control of local homeostasis (9). In the mouse, oral delivery of exogenous SIgA comprising human SC and mouse IgA induced hSC-specific Ab and cellular responses in mucosal and peripheral tissues (10). This occurred in the absence of the prototype mucosal adjuvant cholera toxin.…”

mentioning

confidence: 99%

Secretory IgA Mediates Bacterial Translocation to Dendritic Cells in Mouse Peyer’s Patches with Restriction to Mucosal Compartment

Kadaoui

Corthésy

2007

The Journal of Immunology

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148

127

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In addition to fulfilling its function of immune exclusion at mucosal surfaces, secretory IgA (SIgA) Ab exhibits the striking feature to adhere selectively to M cells in the mouse and human intestinal Peyer’s patches (PPs). Subsequent uptake drives the SIgA Ab to dendritic cells (DCs), which become partially activated. Using freshly isolated mouse DCs, we found that the interaction with SIgA was tissue and DC subtype dependent. Only DCs isolated from PPs and mesenteric lymph nodes interacted with the Ab. CD11c+CD11b+ DCs internalized SIgA, while CD11c+CD19+ DCs only bound SIgA on their surface, and no interaction occurred with CD11c+CD8α+ DCs. We next examined whether SIgA could deliver a sizeable cargo to PP DCs in vivo by administering SIgA-Shigella flexneri immune complexes into a mouse ligated intestinal loop containing a PP. We found that such immune complexes entered the PPs and were internalized by subepithelial dome PP DCs, in contrast to S. flexneri alone that did not penetrate the intestinal epithelium in mice. Dissemination of intraepithelial S. flexneri delivered as immune complexes was limited to PPs and mesenteric lymph nodes. We propose that preexisting SIgA Abs associated with microbes contribute to mucosal defense by eliciting responses that prevent overreaction while maintaining productive immunity.

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Secretory IgA Possesses Intrinsic Modulatory Properties Stimulating Mucosal and Systemic Immune Responses

Cited by 99 publications

References 58 publications

Potentiation of Polarized Intestinal Caco-2 Cell Responsiveness to Probiotics Complexed with Secretory IgA

Potentiation of Polarized Intestinal Caco-2 Cell Responsiveness to Probiotics Complexed with Secretory IgA

Roundtrip Ticket for Secretory IgA: Role in Mucosal Homeostasis?

Secretory IgA Mediates Bacterial Translocation to Dendritic Cells in Mouse Peyer’s Patches with Restriction to Mucosal Compartment

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