Oral Tolerance Can Be Established via Gap Junction Transfer of Fed Antigens from CX3CR1+ Macrophages to CD103+ Dendritic Cells

Mazzini, Elisa; Massimiliano, Lucia; Penna, Giuseppe; Rescigno, María

doi:10.1016/j.immuni.2013.12.012

Cited by 382 publications

(417 citation statements)

References 45 publications

(71 reference statements)

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“…147,164 In the case of protein antigen, this transfer process has been suggested to involve Connexin 43 (Cx43) mediated gap junctions formed between m and cDC and leads to the induction of oral tolerance. 164 Division of labour amongst intestinal m and CD103 + cDC of this kind has also been suggested to be involved in the induction of local Th17 responses to SFB.…”

Section: Macrophages and Induction Of Adaptive Immune Responsesmentioning

confidence: 99%

Diversity and functions of intestinal mononuclear phagocytes

et al. 2017

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Section: Macrophages and Induction Of Adaptive Immune Responsesmentioning

confidence: 99%

Diversity and functions of intestinal mononuclear phagocytes

et al. 2017

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“…+ DCs collaborate in a fascinating way to capture soluble food Ags [156] and induce oral tolerance. In addition, ILC3s control the production of cytokines important for control of fungal burden, such as IL-17 and IL-22 [157].…”

Section: Fungi Inhabiting the Gi Mucosal Surface: The Gut Mycobiotamentioning

confidence: 99%

Richness and diversity of mammalian fungal communities shape innate and adaptive immunity in health and disease

2014

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Human holobiomes are networks of mutualistic interactions between human cells and complex communities of bacteria and fungi that colonize the human body. The immune system must tolerate colonization with commensal bacteria and fungi but defend against invasion by either organism. Molecular ecological surveys of the human prokaryotic microbiota performed to date have revealed a remarkable degree of bacterial diversity and functionality. However, there is a dearth of information regarding the eukaryotic composition of the microbiota. In this review, we describe the ecology and the human niches of our fungal "fellow travelers" in both health and disease, discriminating between passengers, colonizers, and pathogens based on the interaction of these fungi with the human immune system. We conclude by highlighting the need to reconsider the etiology of many fungal and immune-related diseases in the context of the crosstalk between the human system and its resident microbial communities.Keywords: Dysbiosis r Fungal metagenomics r Host-microbe interaction r Mycobiota IntroductionHumans live in close association with a complex community of bacteria, viruses, fungi, and archaea [1][2][3], which inhabit their bodies. Many groups have surveyed these microbial populations using the so-called "next generation" or "deep" sequencing approaches, revealing that the human microbiota differs radically at various body sites and among individuals [2][3][4]. The differences in the human microbiota are influenced by the availability of nutrients, environmental exposure to microorganisms, and other sitespecific features, such as the immunological makeup of a given location. The origin of differences in the microbiota between individuals potentially reflects different patterns of colonization early in life (reviewed in [5]), different dietary regimens [6,7], and different environmental exposures, such as antibiotic use [8,9]. Recently, the application of deep sequencing approaches have genCorrespondence: Dr. Duccio Cavalieri e-mail: duccio.cavalieri@fmach.it erated novel hypotheses about the microbial determinants underlying human disorders of immune origin (reviewed in [10]). Several metabolites of the interaction between diet and host microbiota, such as short-chain fatty acids, have been shown to play a fundamental role in shaping immune responses (reviewed in [11]). The application of microbial ecology concepts is ultimately leading to the conclusion that health and disease can be understood only through an understanding of the ways in which the symbiotic interactions between microbes and human organs harmonically integrate in the context of the hologenome [12].Human microbial diversity is not limited to bacteria; microorganisms such as fungi also play major roles in the stability of microbial communities in human health and disease (reviewed in [13]). Yeasts were detected in human stool samples as far back as 1917, and by the mid-20th century the presence of yeasts in the human intestine was proposed to have a saprotrophic role [14]....

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“…After capturing intraluminal antigen through transepithelial dendrites, CX3CR1 + macrophages transfer antigen to CD103 + DCs, which migrate to mesenteric lymph nodes (MLNs) to serve as antigenpresenting cells (APCs) for the generation of Foxp3 + Treg cells [6,7]. Besides MHC-II-restricted cognate T-DC interactions, this process involves release of TGF-β by DCs and conversion of dietary vitamin A into a tolerogenic metabolite known as retinoic acid (RA) in DCs [7].…”

mentioning

confidence: 99%

“…Considering that ILC3 crosstalk with CD103 + DCs via GM-CSF, MHC-II + ILC3 may capture antigen from CD103 + DCs in MLNs [8]. Alternatively, MHC-II + ILC3 may migrate to MLNs after acquiring antigen from CX3CR1 + macrophages or CD103 + DCs from the gut lamina propria [6]. Accordingly, ILC3 can home to mucosal draining lymph nodes by following chemotactive gradients established by CCR7 ligands [11].…”

mentioning

confidence: 99%