Secretory immunoglobulin A: well beyond immune exclusion at mucosal surfaces

2008 ◽  
Vol 31 (2) ◽  
pp. 174-179 ◽  
Author(s):  
Blaise Corthësy
Keyword(s):  
Immunoglobulin A ◽  
Secretory Immunoglobulin A ◽  
Mucosal Surfaces ◽  
Immune Exclusion ◽  
Secretory Immunoglobulin

scholarly journals Cleavage of the Human Immunoglobulin A1 (IgA1) Hinge Region by IgA1 Proteases Requires Structures in the Fc region of IgA

2003 ◽  
Vol 71 (5) ◽  
pp. 2563-2570 ◽  
Author(s):  
Koteswara R. Chintalacharuvu ◽  
Philip D. Chuang ◽  
Ashley Dragoman ◽  
Christine Z. Fernandez ◽  
Jiazhou Qiu ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Pathogenic Bacteria ◽  
Immunoglobulin A ◽  
Secretory Immunoglobulin A ◽  
Constant Region ◽  
Wild Type ◽  
Mucosal Surfaces ◽  
Secretory Immunoglobulin

ABSTRACT Secretory immunoglobulin A (IgA) protects the mucosal surfaces against inhaled and ingested pathogens. Many pathogenic bacteria produce IgA1 proteases that cleave in the hinge of IgA1, thus separating the Fab region from the Fc region and making IgA ineffective. Here, we show that Haemophilus influenzae type 1 and Neisseria gonorrhoeae type 2 IgA1 proteases cleave the IgA1 hinge in the context of the constant region of IgA1 or IgA2m(1) but not in the context of IgG2. Both Cα2 and Cα3 but not Cα1 are required for the cleavage of the IgA1 hinge by H. influenzae and N. gonorrhoeae proteases. While there was no difference in the cleavage kinetics between wild-type IgA1 and IgA1 containing only the first GalNAc residue of the O-linked glycans, the absence of N-linked glycans in the Fc increased the ability of the N. gonorrhoeae protease to cleave the IgA1 hinge. Taken together, these results suggest that, in addition to the IgA1 hinge, structures in the Fc region of IgA are required for the recognition and cleavage of IgA1 by the H. influenzae and N. gonorrhoeae proteases.

scholarly journals Specialization of mucosal immunoglobulins in pathogen control and microbiota homeostasis occurred early in vertebrate evolution

2020 ◽  
Vol 5 (44) ◽  
pp. eaay3254 ◽  
Author(s):  
Zhen Xu ◽  
Fumio Takizawa ◽  
Elisa Casadei ◽  
Yasuhiro Shibasaki ◽  
Yang Ding ◽  
...  
Keyword(s):  
Rainbow Trout ◽  
Tissue Damage ◽  
Immunoglobulin A ◽  
Secretory Immunoglobulin A ◽  
Central Question ◽  
Vertebrate Species ◽  
Mucosal Surfaces ◽  
Pathogen Control ◽  
Mucosal Pathogens ◽  
Secretory Immunoglobulin

Although mammalian secretory immunoglobulin A (sIgA) targets mucosal pathogens for elimination, its interaction with the microbiota also enables commensal colonization and homeostasis. This paradoxical requirement in the control of pathogens versus microbiota raised the question of whether mucosal (secretory) Igs (sIgs) evolved primarily to protect mucosal surfaces from pathogens or to maintain microbiome homeostasis. To address this central question, we used a primitive vertebrate species (rainbow trout) in which we temporarily depleted its mucosal Ig (sIgT). Fish devoid of sIgT became highly susceptible to a mucosal parasite and failed to develop compensatory IgM responses against it. IgT depletion also induced a profound dysbiosis marked by the loss of sIgT-coated beneficial taxa, expansion of pathobionts, tissue damage, and inflammation. Restitution of sIgT levels in IgT-depleted fish led to a reversal of microbial translocation and tissue damage, as well as to restoration of microbiome homeostasis. Our findings indicate that specialization of sIgs in pathogen and microbiota control occurred concurrently early in evolution, thus revealing primordially conserved principles under which primitive and modern sIgs operate in the control of microbes at mucosal surfaces.

scholarly journals The immune landscape of IgA induction in the gut

2021 ◽  
Author(s):  
Claudia Seikrit ◽  
Oliver Pabst
Keyword(s):  
Protective Immunity ◽  
Immunoglobulin A ◽  
Antibody Responses ◽  
Dark Side ◽  
Secretory Immunoglobulin A ◽  
Antibody Isotype ◽  
Mucosal Antibody ◽  
Key Concepts ◽  
Basic Understanding ◽  
Secretory Immunoglobulin

AbstractAntibodies are key elements of protective immunity. In the mucosal immune system in particular, secretory immunoglobulin A (SIgA), the most abundantly produced antibody isotype, protects against infections, shields the mucosal surface from toxins and environmental factors, and regulates immune homeostasis and a peaceful coexistence with our microbiota. However, the dark side of IgA biology promotes the formation of immune complexes and provokes pathologies, e.g., IgA nephropathy (IgAN). The precise mechanisms of how IgA responses become deregulated and pathogenic in IgAN remain unresolved. Yet, as the field of microbiota research moved into the limelight, our basic understanding of IgA biology has been taking a leap forward. Here, we discuss the structure of IgA, the anatomical and cellular foundation of mucosal antibody responses, and current concepts of how we envision the interaction of SIgA and the microbiota. We center on key concepts in the field while taking account of both historic findings and exciting new observations to provide a comprehensive groundwork for the understanding of IgA biology from the perspective of a mucosal immunologist.

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