Antibiotics promote the sampling of luminal antigens and bacteria via colonic goblet cell associated antigen passages

Knoop, Kathryn A.; Gustafsson, Jenny; McDonald, Keely G.; Kulkarni, Devesha H.; Kassel, Rachel; Newberry, Rodney D.

doi:10.1080/19490976.2017.1299846

Cited by 55 publications

(69 citation statements)

References 43 publications

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“…i–k), indicating that CCR6 was promoting interactions with the epithelium. We never observed CD11c + cells extending dendrites into the lumen in wildtype or CCR6 −/− mice, consistent with prior observations that this is a rare event in the steady state when the mucus barrier is intact …”

Section: Resultssupporting

confidence: 92%

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CCR6 promotes steady‐state mononuclear phagocyte association with the intestinal epithelium, imprinting and immune surveillance

et al. 2017

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The intestinal lamina propria (LP) contains antigen-presenting cells with features of dendritic cells and macrophages, collectively referred to as mononuclear phagocytes (MNPs). Association of MNPs with the epithelium is thought to play an important role in multiple facets of intestinal immunity including imprinting MNPs with the ability to induce IgA production, inducing the expression of gut homing molecules on T cells, facilitating the capture of luminal antigens and microbes, and subsequent immune responses in the mesenteric lymph node (MLN). However, the factors promoting this process in the steady state are largely unknown, and in vivo models to test and confirm the importance of LP-MNP association with the epithelium for these outcomes are unexplored. Evaluation of epithelial expression of chemoattractants in mice where MNP-epithelial associations were impaired suggested CCL20 as a candidate promoting epithelial association. Expression of CCR6, the only known receptor for CCL20, was required for MNPs to associate with the epithelium. LP-MNPs from CCR6 mice did not display defects in acquiring antigen and stimulating T-cell responses in ex vivo assays or in responses to antigen administered systemically. However, LP-MNPs from CCR6-deficient mice were impaired at acquiring luminal and epithelial antigens, inducing IgA production in B cells, inducing immune responses in the MLN, and capturing and trafficking luminal commensal bacteria to the MLN. These findings identify a crucial role for CCR6 in promoting LP-MNPs to associate with the intestinal epithelium in the steady state to perform multiple functions promoting gut immune homeostasis.

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Section: Resultssupporting

confidence: 92%

“…Evaluation of bacterial translocation to the MLN was performed as previously described . Mice were gavaged with 500 mg ampicillin, 500 mg metronidazole, 500 mg neomycin and 250 mg vancomycin and colon‐draining MLNs were isolated 4 days later.…”

Section: Methodsmentioning

confidence: 99%

CCR6 promotes steady‐state mononuclear phagocyte association with the intestinal epithelium, imprinting and immune surveillance

et al. 2017

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“…S4). Studies evaluating TED formation in adult mice removed luminal contents and mucus prior to imaging (30–32, 35, 36), a process, which induces TED formation in the SI, but not the colon of adult mice (34). We observed that even after removal of the luminal contents and mucus layer, TEDs did not form in the SI or colon of DOL18 mice (Fig.…”

Section: Resultsmentioning

confidence: 99%

Microbial antigen encounter during a preweaning interval is critical for tolerance to gut bacteria

et al. 2017

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We have a mutually beneficial relationship with the trillions of microorganisms inhabiting our gastrointestinal tract. However, maintaining this relationship requires recognizing these organisms as affable and restraining inflammatory responses to these organisms when encountered in hostile settings. How and when the immune system develops tolerance to our gut microbial members is not well understood. Here we identify a specific pre-weaning interval in which gut microbial antigens are encountered by the immune system to induce antigen specific tolerance to gut bacteria. Intriguingly for some bacterial taxa, physiologic encounters with the immune system are restricted to this interval, despite abundance of these taxa in the gut lumen at later times outside this interval. Antigen specific tolerance to gut bacteria induced during this pre-weaning interval is stable and maintained even if these taxa are encountered later in life in an inflammatory setting. However, inhibiting microbial antigen encounter during this interval or extending these encounters beyond the normal interval, results in a failure to induce tolerance and robust antigen specific effector responses to gut bacteria upon reencounter in an inflammatory setting. Thus, we have identified a defined pre-weaning interval critical for developing tolerance to gut bacteria and maintaining the mutually beneficial relationship with our gut microbiota.

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“…Furthermore, luminal exposure to an invasive S . Typhimurium, shut off GAP‐associated translocation suggesting that goblet cell sensing of an invasive pathogen to shut off GAPs is a host defence mechanism (Kulkarni et al ., ; Knoop et al ., ).…”

Section: The Microbiota Influences Gut Biologymentioning

confidence: 97%

“…Deletion of goblet cells in a mouse model of wild type Salmonella Typhimurium infection prevented the translocation bacteria to the draining mesenteric lymph nodes, indicating that S. Typhimurium uses goblet cells as an entry portal. Furthermore, luminal exposure to an invasive S. Typhimurium, shut off GAP-associated translocation suggesting that goblet cell sensing of an invasive pathogen to shut off GAPs is a host defence mechanism (Kulkarni et al, 2016;Knoop et al, 2017).…”

Section: Microbial Targeting Of Epithelial Immune Defencesmentioning

confidence: 99%

Host‐microbe interaction in the gastrointestinal tract

Parker

Lawson

Vaux

et al. 2017

Environmental Microbiology

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SummaryThe gastrointestinal tract is a highly complex organ in which multiple dynamic physiological processes are tightly coordinated while interacting with a dense and extremely diverse microbial population. From establishment in early life, through to host‐microbe symbiosis in adulthood, the gut microbiota plays a vital role in our development and health. The effect of the microbiota on gut development and physiology is highlighted by anatomical and functional changes in germ‐free mice, affecting the gut epithelium, immune system and enteric nervous system. Microbial colonisation promotes competent innate and acquired mucosal immune systems, epithelial renewal, barrier integrity, and mucosal vascularisation and innervation. Interacting or shared signalling pathways across different physiological systems of the gut could explain how all these changes are coordinated during postnatal colonisation, or after the introduction of microbiota into germ‐free models. The application of cell‐based in‐vitro experimental systems and mathematical modelling can shed light on the molecular and signalling pathways which regulate the development and maintenance of homeostasis in the gut and beyond.

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Antibiotics promote the sampling of luminal antigens and bacteria via colonic goblet cell associated antigen passages

Cited by 55 publications

References 43 publications

CCR6 promotes steady‐state mononuclear phagocyte association with the intestinal epithelium, imprinting and immune surveillance

CCR6 promotes steady‐state mononuclear phagocyte association with the intestinal epithelium, imprinting and immune surveillance

Microbial antigen encounter during a preweaning interval is critical for tolerance to gut bacteria

Host‐microbe interaction in the gastrointestinal tract

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