Secretory IgA in the Coordination of Establishment and Maintenance of the Microbiota

Pabst, Oliver; Cerovic, Vuk; Hornef, Mathias W.

doi:10.1016/j.it.2016.03.002

Cited by 162 publications

(138 citation statements)

References 73 publications

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“…SIgA mainly acts as a neutralizing agent by binding to micro-organisms and thereby preventing pathogen attachment and invasion of the intestinal epithelium. The additional antiinflammatory roles of secretory IgA have been extensively reviewed by others [11,12]. Serum IgA is a monomeric molecule, which has either anti-or pro-inflammatory roles depending on the circumstances [13,14].…”

Section: Iga and Fcarimentioning

confidence: 99%

Immunoglobulin A: magic bullet or Trojan horse?

Heineke

Egmond

2017

Eur J Clin Investigation

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Background Neutrophils participate in the first line of defense by executing several killing mechanisms, including phagocytosis, degranulation and the release of neutrophil extracellular traps. Additionally, they can orchestrate the adaptive immune system by secreting cytokines and chemokines. Opsonization with antibodies aids in the recognition of pathogens, via binding to Fc receptors on the neutrophil surface. Immunoglobulin A (IgA) is the most abundant antibody at mucosal sites and has multiple functions in homeostasis and immunity. Neutrophils and IgA can interact via the IgA Fc receptor FcRI (CD89), leading to pro-or anti-inflammatory responses.

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Section: Iga and Fcarimentioning

confidence: 99%

Immunoglobulin A: magic bullet or Trojan horse?

Heineke

Egmond

2017

Eur J Clin Investigation

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“…IgA anti‐PDC‐E2 antibodies have been detected not only in serum but also in bile, saliva, and urine; and the presence of IgA anti‐PDC‐E2 in serum and in saliva has been associated with histological progression of PBC . Biliary epithelial cells have the capacity to export dimeric IgA to the bile through polymeric Ig receptor–mediated transcytosis . Our data demonstrate that the majority of PDC‐E2‐specific and PDC‐E2/xenobiotic–cross‐reactive plasmablasts (75% and 58%, respectively) are IgA.…”

Section: Discussionmentioning

confidence: 73%

Autoreactive monoclonal antibodies from patients with primary biliary cholangitis recognize environmental xenobiotics

et al. 2017

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A major problem in autoimmunity has been identification of the earliest events that lead to breach of tolerance. Although there have been major advances in dissecting effector pathways and the multi-lineage immune responses to mitochondrial self-antigens in primary biliary cholangitis (PBC), the critical links between environmental factors and tolerance remain elusive. We hypothesized that environmental xenobiotic modification of the E2 subunit of the pyruvate dehydrogenase (PDC-E2) inner lipoyl domain can lead to loss of tolerance to genetically susceptible hosts. Previously we demonstrated that serum anti-PDC-E2 autoantibodies cross-react with the chemical xenobiotics 2-octynoic acid (2-OA) and 6,8-bis (acetylthio) octanoic acid (SAc) and further that there is a high frequency of PDC-E2 specific peripheral plasmablasts. Herein we generated 104 recombinant mAbs based on paired heavy- and light-chain variable regions of individual plasmablasts derived from PBC patients. We identified 32 mAbs reactive with native PDC-E2, including 20 specific for PDC-E2 and 12 cross-reactive with both PDC-E2 and 2-OA and SAc. A lower frequency of replacement somatic hypermutations, indicating lower level of affinity maturation, was observed in the complementarity-determining regions (CDR) of the cross-reactive mAbs in comparison to mAbs exclusively recognizing PDC-E2 or those for irrelevant antigens. In particular, when the highly mutated heavy chain gene of a cross-reactive mAb was reverted to the germline sequence, the PDC-E2 reactivity was reduced dramatically whereas the xenobiotics reactivity was retained. Importantly, cross-reactive mAbs also recognized lipoic acid (LA), a mitochondrial fatty acid that is covalently bound to PDC-E2. Our data reflect that chemically modified LA or LA itself, via molecular mimicry, is the initial target that leads to the development of PBC.

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“…It has been proposed that coating of commensal bacteria by sIgA may lead to a different recognition by epithelial cells and dendritic cells as compared to pathogens, and hence faciliate the discrimmination between symbionts and pathogens by the host (Sansonetti, 2011). Indeed, recent studies indicate that sIgA plays a role in shaping and maintaining the gut microbiota from birth to adulthood (Pabst et al , 2016). Neutralizaton of bacterial toxins is another function of IgA (Vaerman et al , 1985, Forbes et al , 2011).…”

Section: Secretory Immunoglobulin a (Siga)mentioning

confidence: 99%

Defensins, lectins, mucins, and secretory immunoglobulin A: microbe-binding biomolecules that contribute to mucosal immunity in the human gut

Chairatana

Nolan

2016

Critical Reviews in Biochemistry and Molecular Biology

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In the intestine, the mucosal immune system plays essential roles in maintaining homeostasis between the host and microorganisms, and protecting the host from pathogenic invaders. Epithelial cells produce and release a variety of biomolecules into the mucosa and lumen that contribute to immunity. In this review, we focus on a subset of these remarkable host-defense factors – enteric α-defensins, select lectins, mucins, and secretory immunoglobulin A – that have the capacity to bind microbes and thereby contribute to barrier function in the human gut. We provide an overview of the intestinal epithelium, describe specialized secretory cells named Paneth cells, and summarize our current understanding of the biophysical and functional properties of these select microbe-binding biomolecules. We intend for this compilation to complement prior reviews on intestinal host-defense factors, highlight recent advances in the field, and motivate investigations that further illuminate molecular mechanisms as well as the interplay between these molecules and microbes.

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Secretory IgA in the Coordination of Establishment and Maintenance of the Microbiota

Cited by 162 publications

References 73 publications

Immunoglobulin A: magic bullet or Trojan horse?

Immunoglobulin A: magic bullet or Trojan horse?

Autoreactive monoclonal antibodies from patients with primary biliary cholangitis recognize environmental xenobiotics

Defensins, lectins, mucins, and secretory immunoglobulin A: microbe-binding biomolecules that contribute to mucosal immunity in the human gut

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