Gastrointestinal manifestations in primary immune disorders

Agarwal, Shradha; Mayer, Lloyd

doi:10.1002/ibd.21040

Cited by 56 publications

(39 citation statements)

References 92 publications

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“…*P < 0.05, **P < 0.01, ***P < 0.001. (26,27), indicating that this type of relationship is tightly controlled. Second, microbial communities are very complex, making it difficult to identify specific lineages that could be beneficial or detrimental.…”

Section: Discussionmentioning

confidence: 99%

Microbiota regulates type 1 diabetes through Toll-like receptors

Burrows

Volchkov

Kobayashi

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

158

125

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Deletion of the innate immune adaptor myeloid differentiation primary response gene 88 (MyD88) in the nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D) results in microbiota-dependent protection from the disease: MyD88-negative mice in germfree (GF), but not in specific pathogen-free conditions develop the disease. These results could be explained by expansion of particular protective bacteria ("specific lineage hypothesis") or by dominance of negative (tolerizing) signaling over proinflammatory signaling ("balanced signal hypothesis") in mutant mice. Here we found that colonization of GF mice with a variety of intestinal bacteria was capable of reducing T1D in MyD88-negative (but not wild-type NOD mice), favoring the balanced signal hypothesis. However, the receptors and signaling pathways involved in prevention or facilitation of the disease remained unknown. The protective signals triggered by the microbiota were revealed by testing NOD mice lacking MyD88 in combination with knockouts of several critical components of innate immune sensing for development of T1D. Only MyD88-and TIR-domain containing adapter inducing IFN β (TRIF) double deficient NOD mice developed the disease. Thus, TRIF signaling (likely downstream of Toll-like receptor 4, TLR4) serves as one of the microbiota-induced tolerizing pathways. At the same time another TLR (TLR2) provided prodiabetic signaling by controlling the microbiota, as reduction in T1D incidence caused by TLR2 deletion was reversed in GF TLR2-negative mice. Our results support the balanced signal hypothesis, in which microbes provide signals that both promote and inhibit autoimmunity by signaling through different receptors, including receptors of the TLR family.Toll-like receptors | commensal microbiota | type 1 diabetes

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Section: Discussionmentioning

confidence: 99%

Microbiota regulates type 1 diabetes through Toll-like receptors

Burrows

Volchkov

Kobayashi

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

158

125

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“…Patients with chronic granulomatous disease, which involves defects in the ROS pathway, have a predisposition to colitis. 22 …”

Section: Intestinal Immune Defenses Against Microbiotamentioning

confidence: 99%

Interactions Between the Host Innate Immune System and Microbes in Inflammatory Bowel Disease

2011

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The intestinal immune system defends against pathogens and entry of excessive intestinal microbes; simultaneously, a state of immune tolerance to resident intestinal microbes must be maintained. Perturbation of this balance is associated with intestinal inflammation in various mouse models and is thought to predispose humans to inflammatory bowel disease (IBD). The innate immune system senses microbes; dendritic cells, macrophages, and epithelial cells produce an initial, rapid response. The immune system continuously monitors resident microbiota and utilizes constitutive antimicrobial mechanisms to maintain immune homeostasis. associations between IBD and genes that regulate microbial recognition and innate immune pathways, such as nucleotide oligomerization domain 2 (Nod2), genes that control autophagy (eg, ATG16L1, IRGM), and genes in the interleukin-23–T helper cell 17 pathway indicate the important roles of host-microbe interactions in regulating intestinal immune homeostasis. There is increasing evidence that intestinal microbes influence host immune development, immune responses, and susceptibility to human diseases such as IBD, diabetes mellitus, and obesity. Conversely, host factors can affect microbes, which in turn modulate disease susceptibility. We review the cell populations and mechanisms that mediate interactions between host defense and tolerance and how the dysregulation of host-microbe interactions leads to intestinal inflammation and IBD.

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“…Considering that the gastrointestinal tract is the largest lymphoid organ in the body, continuously exposed to antigen derived from food and bacteria [57], it is not surprising that many children with primary immunodeficiencies develop gastrointestinal symptoms [58]. Note the gastrointestinal manifestations may be the initial presentation of PID.…”

Section: Acute and Chronic Food Protein-induced Enterocolitis Syndromementioning

confidence: 99%

Differential diagnosis of food protein-induced enterocolitis syndrome

Fiocchi

Claps

Dahdah

et al. 2014

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of reviewTo assess all the possible differential diagnosis of food protein-induced enterocolitis syndrome (FPIES), both in acute and chronic presentation, reviewing the data reported in published studies.Recent findingsThere is an increase of reported cases of FPIES in recent years. As the disease presents with nonspecific symptoms, it can be misunderstood in many ways. The differential diagnosis includes, in acute presentations, the following: sepsis, other infectious diseases, acute gastrointestinal episodes, surgical emergencies, food allergies. In its chronic forms, FPIES may mimic malabsorption syndromes, metabolic disorders, primary immunodeficiencies, neurological conditions, coagulation defects, and other types of non-IgE-mediated food allergy.SummaryA thorough clinical evaluation, including symptoms, signs, and laboratory findings, is necessary to lead the clinicians toward the diagnosis of FPIES. The major reason for delayed diagnosis appears to be the lack of knowledge of the disease.

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Gastrointestinal manifestations in primary immune disorders

Cited by 56 publications

References 92 publications

Microbiota regulates type 1 diabetes through Toll-like receptors

Microbiota regulates type 1 diabetes through Toll-like receptors

Interactions Between the Host Innate Immune System and Microbes in Inflammatory Bowel Disease

Differential diagnosis of food protein-induced enterocolitis syndrome

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