Anti-commensal Ig—from enormous diversity to clear function

Rollenske, Tim

doi:10.1038/s41385-019-0223-8

Cited by 6 publications

(4 citation statements)

References 19 publications

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“…Nevertheless, T cell‐independent pathways may contribute during early life when the commensal microbiota is established 235 . If future efforts in understanding IgA induction, production, and responses, it is important for researcher to be more careful in differentiating these scenarios 236 . Germ‐free mice reconstituted with a microbiota or immunodeficient mice into which purified cells are transferred are likely to be affected by homeostatic effects and/or redundancy and will be poor proxies of the situation in normal adult individuals already reacting to a complex microbiota.…”

Section: Discussionmentioning

confidence: 99%

“… 235 If future efforts in understanding IgA induction, production, and responses, it is important for researcher to be more careful in differentiating these scenarios. 236 Germ-free mice reconstituted with a microbiota or immunodeficient mice into which purified cells are transferred are likely to be affected by homeostatic effects and/or redundancy and will be poor proxies of the situation in normal adult individuals already reacting to a complex microbiota. For researchers studying mucosal immunology to eventually reach a consensus view on how the IgA system protects against pathogens but at the same time maintains the commensal microbiota, it is important to perform studies in systems that resembles physiological conditions.…”

Section: Discussionmentioning

confidence: 99%

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Know your enemy or find your friend?—Induction of IgA at mucosal surfaces

Bemark

Angeletti

2021

Immunological Reviews

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Most antibodies produced in the body are of the IgA class. The dominant cell population producing them are plasma cells within the lamina propria of the gastrointestinal tract, but many IgA‐producing cells are also found in the airways, within mammary tissues, the urogenital tract and inside the bone marrow. Most IgA antibodies are transported into the lumen by epithelial cells as part of the mucosal secretions, but they are also present in serum and other body fluids. A large part of the commensal microbiota in the gut is covered with IgA antibodies, and it has been demonstrated that this plays a role in maintaining a healthy balance between the host and the bacteria. However, IgA antibodies also play important roles in neutralizing pathogens in the gastrointestinal tract and the upper airways. The distinction between the two roles of IgA ‐ protective and balance‐maintaining ‐ not only has implications on function but also on how the production is regulated. Here, we discuss these issues with a special focus on gut and airways.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Know your enemy or find your friend?—Induction of IgA at mucosal surfaces

Bemark

Angeletti

2021

Immunological Reviews

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“…However, the specific bacterial taxa that drive or exacerbate MS and the mechanisms by which those bacteria influence host immunity remain unclear. Immunoglobulin A (IgA), produced mostly at mucosal surfaces, is the predominant antibody isotype in humans and functions as a critical mediator of intestinal homeostasis (12)(13)(14)(15). Mounting evidence suggests a major effect of mucosal microbiota in shaping the IgA + B cell repertoire (16).…”

Section: Introductionmentioning

confidence: 99%

Gut microbiota–specific IgA ⁺ B cells traffic to the CNS in active multiple sclerosis

et al. 2020

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Changes in gut microbiota composition and a diverse role of B cells have recently been implicated in multiple sclerosis (MS), a central nervous system (CNS) autoimmune disease. Immunoglobulin A (IgA) is a key regulator at the mucosal interface. However, whether gut microbiota shape IgA responses and what role IgA+ cells have in neuroinflammation are unknown. Here, we identify IgA-bound taxa in MS and show that IgA-producing cells specific for MS-associated taxa traffic to the inflamed CNS, resulting in a strong, compartmentalized IgA enrichment in active MS and other neuroinflammatory diseases. Unlike previously characterized polyreactive anti-commensal IgA responses, CNS IgA cross-reacts with surface structures on specific bacterial strains but not with brain tissue. These findings establish gut microbiota–specific IgA+ cells as a systemic mediator in MS and suggest a critical role of mucosal B cells during active neuroinflammation with broad implications for IgA as an informative biomarker and IgA-producing cells as an immune subset to harness for therapeutic interventions.

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“…Antibodies play a vital role in homeostasis and protective immunity at mucosal sites, as well as during systemic infections 46 , 47 , and can be divided into five isotypes, which operate in distinct places and have distinct effector functions 48 . Antibody effector functions have classically been studied in the context of pathogenic infections 49 . However, it is apparent that luminal and serum antibodies bind members of the microbiota 50 .…”

Section: Antibody-mediated Immunity Against C Albicansmentioning

confidence: 99%

Immunosurveillance of Candida albicans commensalism by the adaptive immune system

Swidergall

LeibundGut‐Landmann

2022

Mucosal Immunology

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The fungal microbiota (mycobiota) is an integral part of the microbial community colonizing the body surfaces and is involved in many key aspects of human physiology, while an imbalance of the fungal communities, termed fungal dysbiosis, has been described in pathologies ranging from infections to inflammatory bowel disease. Commensal organisms, such as the fungus Candida albicans, induce antigen-specific immune responses that maintain immune homeostasis. Adaptive immune mechanisms are vital in this process, while deficiencies in adaptive immunity are linked to fungal infections. We start to understand the mechanisms by which a shift in mycobiota composition, in particular in C. albicans abundance, is linked to immunopathological conditions. This review discusses the mechanisms that ensure continuous immunosurveillance of C. albicans during mucosal colonization, how these protective adaptive immune responses can also promote immunopathology, and highlight therapeutic advances against C. albicans-associated disease.

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Anti-commensal Ig—from enormous diversity to clear function

Cited by 6 publications

References 19 publications

Know your enemy or find your friend?—Induction of IgA at mucosal surfaces

Know your enemy or find your friend?—Induction of IgA at mucosal surfaces

Gut microbiota–specific IgA ⁺ B cells traffic to the CNS in active multiple sclerosis

Immunosurveillance of Candida albicans commensalism by the adaptive immune system

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Anti-commensal Ig—from enormous diversity to clear function

Cited by 6 publications

References 19 publications

Know your enemy or find your friend?—Induction of IgA at mucosal surfaces

Know your enemy or find your friend?—Induction of IgA at mucosal surfaces

Gut microbiota–specific IgA + B cells traffic to the CNS in active multiple sclerosis

Immunosurveillance of Candida albicans commensalism by the adaptive immune system

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Product

Resources

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Gut microbiota–specific IgA ⁺ B cells traffic to the CNS in active multiple sclerosis