• IgA
• SIgA
• antibiotics
• breast milk
• breastfeeding
• late-onset sepsis
• mucosal immune system
• neonatal immune system
• pregnancy
• prenatal antibiotics

• Animals
• Mice
• Female
• Pregnancy
• Animals, Newborn
• Anti-Bacterial Agents/pharmacology
• Dysbiosis/microbiology
• Immunoglobulin A
• Sepsis/microbiology
• Sepsis/immunology
• Gastrointestinal Microbiome/drug effects
• Feces/microbiology
• Humans
• Immunoglobulin A, Secretory
• Milk, Human/immunology
• Mice, Inbred C57BL
• Milk
• Disease Susceptibility
• T-Lymphocytes, Regulatory/immunology
• T-Lymphocytes, Regulatory/drug effects
• Apyrase/metabolism
• Intestinal Mucosa/drug effects
• Intestinal Mucosa/immunology
• Intestinal Mucosa/microbiology

• adaptive immunity
• antigen specific immunotherapy (ASIT)
• bronchus associated lymphoid tissue (BALT)
• drug delivery
• germinal center (GC)
• mucosal vaccine
• nasal associated lymphoid tissue (NALT)
• secretory IgA (SIgA)

• Humans
• Animals
• Immunity, Mucosal
• Immunomodulation
• Respiratory Mucosa/immunology
• Respiratory Mucosa/metabolism
• Lymphoid Tissue/immunology
• Vaccines/immunology
• Nasal Mucosa/immunology
• Nasal Mucosa/metabolism
• Administration, Intranasal

• epigenetic
• gut dysbiosis
• inflammation
• metabolic diseases
• microbiome
• microbiota
• oxidative stress
• transgenerational

• Autophagy
• Bioinformatic
• Pathogenesis
• Targets
• Ulcerative colitis

• Allergen specific
• Cytokine
• Dendritic cells
• Food allergy
• In vitro
• T cells

• Humans
• Coculture Techniques
• T-Lymphocytes
• Food Hypersensitivity
• Cytokines
• CD40 Ligand
• Allergens

• Adaptive immunity
• Cytokines
• Gastroenterology
• Immunology
• Tolerance

• B cells
• Mucosa
• allergy
• antibodies
• class switching
• tolerance

• non-digestible carbohydrates
• prebiotics
• short-chain fatty acids (SCFA)

The cornea is an avascular connective tissue that is crucial, not only as the primary barrier of the eye but also as a proper transparent refractive structure. Corneal transparency is necessary for vision and is the result of several factors, including its highly organized structure, the physiology of its few cellular components, the lack of myelinated nerves (although it is extremely innervated), the tightly controlled hydration state, and the absence of blood and lymphatic vessels in healthy conditions, among others. The avascular, immune-privileged tissue of the cornea is an ideal model to study the interactions between its well-characterized and dense sensory nerves (easily accessible for both focal electrophysiological recording and morphological studies) and the low number of resident immune cell types, distinguished from those cells migrating from blood vessels. This paper presents an overview of the corneal structure and innervation, the resident dendritic cell (DC) subpopulations present in the cornea, their distribution in relation to corneal nerves, and their role in ocular inflammatory diseases. A mouse model in which sensory axons are constitutively labeled with tdTomato and DCs with green fluorescent protein (GFP) allows further analysis of the neuro-immune crosstalk under inflammatory and steady-state conditions of the eye.

• animal models
• corneal nerves
• dendritic cells
• neuro-immune interactions
• ocular inflammation
• ocular pain

• Animals
• Cornea/innervation
• Dendritic Cells
• Mice
• Models, Theoretical
• Neuroimmunomodulation

• biochemistry molecular biology clinical biochemistry cancer research oxidative stress
• crohn’s disease (cd)
• inflammatory bowel disease
• ulcerative colıtıs

• Parkinson’s disease
• enteric nervous system
• gut lumen content
• nutrients
• α-synuclein

• Conjunctiva
• Contact lens wear
• Cornea
• Dry eye
• Microbiome
• Microbiota
• Ocular surface
• Tear film

• PPARγ
• acute respiratory distress
• inflammation
• lung injury
• molecular targets

• Animals
• Curcumin/metabolism
• Curcumin/pharmacology
• Eicosanoids/metabolism
• Eicosanoids/pharmacology
• Humans
• Inflammation/metabolism
• Ligands
• Lung Diseases/drug therapy
• Lung Diseases/metabolism
• PPAR gamma/agonists
• PPAR gamma/metabolism
• Protein Processing, Post-Translational/drug effects
• Signal Transduction/drug effects
• Signal Transduction/physiology

Purpose: To evaluate safety and tolerability on the ocular surface of an anti-septic formulation containing 0.6% povidone–iodine (0.6% PVI) for a 4 week period.

Methods: An observational, prospective study included 20 mild-moderate dry eye disease (DED) patients who enrolled at the Ocular Surface Disease Unit of the University of Messina, receiving 0.6% PVI eye drops for 28 days, 2 drops twice daily (BID). The assessment included the Ocular Surface Disease Index questionnaire; symptoms score (0 = absent to 3 = severe) for burning, ocular dryness, foreign body sensation, watery eyes, tearing, photophobia, and ocular pain; fluorescein tear break-up time (TBUT); and corneal-conjunctival staining, performed at baseline (T0), after 7 (T7) and 28 (T28). Schirmer I-test, corneal endothelial cell count, intraocular pressure, and fundus examination were performed at T0 and T28. The main outcome measures were TBUT and corneal-conjunctival staining as markers of ocular surface homeostasis. For statistical analysis, Student's T-test and Wilcoxon test were used as appropriate.

Results: No significant alterations of the safety parameters were found throughout the study. Further, at T28 a significant improvement of burning, ocular dryness, foreign body sensation, and watery eyes (T0 vs. T28 P < 0.03) were observed; corneal-conjunctival staining improved at T28 (T0 vs. T28 P < 0.0001), and TBUT improved already at T7 (T0 vs. T7 P = 0.0008) lasting so till the end of the study. The only adverse event was mild burning at instillation for the first 3 days of treatment in most of the patients.

Conclusions: The treatment with 0.6% PVI was safe and well tolerated in a group of patients with a damaged ocular surface.

• antibiotic resistance
• antiseptic
• dry eye disease
• microbiota
• ocular surface
• povidone–iodine

Beneficial effects of probiotics on gut microbiota homeostasis and inflammatory immune responses suggested the investigation of their potential clinical efficacy in experimental models of autoimmune diseases. Indeed, administration of two bifidobacteria and lactobacilli probiotic strains prevented disease manifestations in the Lewis rat model of Myasthenia Gravis (EAMG). Here, we demonstrate the clinical efficacy of therapeutic administration of vital bifidobacteria (i.e., from EAMG onset). The mechanisms involved in immunomodulation were investigated with ex vivo and in vitro experiments. Improvement of EAMG symptoms was associated to decreased anti-rat AChR antibody levels, and differential expression of TGFβ and FoxP3 immunoregulatory transcripts in draining lymph nodes and spleen of treated-EAMG rats. Exposure of rat bone marrow-derived dendritic cells to bifidobacteria or lactobacilli strains upregulated toll-like receptor 2 mRNA expression, a key molecule involved in bacterium recognition via lipotheicoic acid. Live imaging experiments of AChR-specific effector T cells, co-cultured with BMDCs pre-exposed to bifidobacteria, demonstrated increased percentages of motile effector T cells, suggesting a hindered formation of TCR-peptide-MHC complex. Composition of gut microbiota was studied by 16S rRNA gene sequencing, and α and β diversity were determined in probiotic treated EAMG rats, with altered ratios between Tenericutes and Verrucomicrobia (phylum level), and Ruminococcaceae and Lachnospiraceae (family level). Moreover, the relative abundance of Akkermansia genus was found increased compared to healthy and probiotic treated EAMG rats. In conclusion, our findings confirms that the administration of vital bifidobacteria at EAMG onset has beneficial effects on disease progression; this study further supports preclinical research in human MG to evaluate probiotic efficacy as supplementary therapy in MG.

• EAMG
• MG
• immunoregulation
• probiotics
• therapeutic treatment

• Animals
• Cell Adhesion Molecules/biosynthesis
• Cell Line
• Epithelial Cells/metabolism
• Epithelial Cells/pathology
• Gene Expression Regulation
• Humans
• Intestinal Diseases/etiology
• Intestinal Diseases/metabolism
• Intestinal Diseases/pathology
• Intestinal Mucosa/injuries
• Intestinal Mucosa/metabolism
• Intestinal Mucosa/pathology
• Lectins, C-Type/biosynthesis
• MAP Kinase Signaling System
• Male
• Mice
• Mitogen-Activated Protein Kinase 1/metabolism
• Mitogen-Activated Protein Kinase 3/metabolism
• Receptors, Cell Surface/biosynthesis
• Sepsis/complications
• Sepsis/metabolism
• Sepsis/pathology
• Transcription Factor RelA/metabolism

Inflammation is the mechanism of diseases caused by microbial, autoimmune, allergic, metabolic and physical insults that produce distinct types of inflammatory responses. This aetiologic view of inflammation informs its classification based on a cause‐dependent mechanism as well as a cause‐directed therapy and prevention. The genomic era ushered in a new understanding of inflammation by highlighting the cell's nucleus as the centre of the inflammatory response. Exogenous or endogenous inflammatory insults evoke genomic responses in immune and non‐immune cells. These genomic responses depend on transcription factors, which switch on and off a myriad of inflammatory genes through their regulatory networks. We discuss the transcriptional paradigm of inflammation based on denying transcription factors’ access to the nucleus. We present two approaches that control proinflammatory signalling to the nucleus. The first approach constitutes a novel intracellular protein therapy with bioengineered physiologic suppressors of cytokine signalling. The second approach entails control of proinflammatory transcriptional cascades by targeting nuclear transport with a cell‐penetrating peptide that inhibits the expression of 23 out of the 26 mediators of inflammation along with the nine genes required for metabolic responses. We compare these emerging anti‐inflammatory countermeasures to current therapies. The transcriptional paradigm of inflammation offers nucleocentric strategies for microbial, autoimmune, metabolic, physical and other types of inflammation afflicting millions of people worldwide.

• allergy
• atherosclerosis
• autoimmunity
• diabetes
• genome
• hepatitis
• lung inflammation
• metabolic syndrome
• nuclear transport
• transcription
• trauma

The oral mucosa is a first line of defense against pathogenic organisms and yet tolerates food antigens and resident bacteria. Mucosal epithelial cells are emerging as important regulators of innate and adaptive immune responses. However, the contribution of oral epithelial cells (OECs) determining oral immunity is understudied. Here, we evaluated the ability of H413 and TR146 cells, two OEC lines derived from human oral squamous cell carcinomas, and primary OECs to modulate immune responses to a cocktail of Gram⁺ and Gram⁻ bacteria known as MV130. OECs expressed CD40 constitutively and class II major histocompatibility complex (MHC II) molecules when stimulated with IFNγ, but not CD80 or CD86. Dendritic cells (DCs) treated with bacteria in co-culture with OECs did not fully mature, as judged by the expression of MHC II, CD80 and CD86, and barely released IL-12 and TNFα, compared to control DCs. Furthermore, in the presence of OECs, DCs were unable to stimulate allogenic naive CD4 T cells to produce IFNγ and TNFα. Similarly, OECs in culture with total CD4 T cells or Th1 cells stimulated with anti-CD3 and anti-CD28 antibodies abrogated CD25 and CD69 expression, T cell proliferation and the release of IFNγ and TNFα. The inhibition on T cell activation by OECs was cell-contact dependent, TGFβ independent and largely irreversible. Overall, this behavior of OECs is likely key to avoid immune system over-reaction against resident bacteria.

• T cells
• bacteria
• dendritic cells
• immunomodulation
• oral epithelial cells

• Animals
• Anti-Bacterial Agents/pharmacology
• Arthritis, Experimental/drug therapy
• Arthritis, Experimental/immunology
• Gastrointestinal Microbiome/drug effects
• Helminth Proteins/pharmacology
• Helminth Proteins/therapeutic use
• Immunomodulation
• Male
• Mice

• DC
• cancer combination therapies
• cancer vaccines
• human dendritic cells
• mo-DC
• monocyte-derived dendritic cells

• Multiple sclerosis
• Tregs
• bacteria as drug (brug)
• experimental autoimmune encephalomyelitis (EAE)
• gut dysbiosis
• gut microbiota
• immunomodulation
• treatment

• Animals
• Dysbiosis/diet therapy
• Dysbiosis/microbiology
• Gastrointestinal Microbiome
• Humans
• Multiple Sclerosis/diet therapy
• Multiple Sclerosis/microbiology
• Prevotella
• Probiotics/therapeutic use

• P30 ES005605 NIEHS NIH HHS
• R01 AI137075 NIAID NIH HHS

• Caco-2
• T-cells
• Toll-like receptors
• dendritic cells
• resistant starches

• Amylose/pharmacology
• Cytokines/biosynthesis
• Dendritic Cells/drug effects
• Dendritic Cells/immunology
• Glucose/pharmacology
• Humans
• Molecular Weight
• Signal Transduction/drug effects
• Signal Transduction/physiology
• Starch/chemistry
• Starch/pharmacology
• THP-1 Cells
• Toll-Like Receptors/physiology

• Age-related macular degeneration
• Dendritic cells
• Macrophages
• Mast cells
• Microglia
• Retinal degeneration
• Retinitis pigmentosa

• Caco-2
• Lactobacillus acidophilus W37
• Salmonella Typhimurium
• dendritic cells
• inulin-type fructans

• Animals
• Eye/immunology
• Homeostasis
• Humans
• Immune Privilege
• Immune Tolerance
• Immunity, Mucosal
• Inflammation/immunology
• Mucous Membrane/immunology

• R01 EY012963 NEI NIH HHS
• R01 EY020889 NEI NIH HHS
• R01 EY024602 NEI NIH HHS

• Animals
• Apoptosis/genetics
• Colitis/metabolism
• Colitis/microbiology
• Colitis/pathology
• Colon/metabolism
• Colon/microbiology
• Colon/pathology
• Epithelial Cells/microbiology
• Epithelial Cells/physiology
• Inflammation/genetics
• Inflammation/metabolism
• Inflammation/microbiology
• Inflammation/pathology
• Inflammatory Bowel Diseases/genetics
• Inflammatory Bowel Diseases/immunology
• Inflammatory Bowel Diseases/metabolism
• Inflammatory Bowel Diseases/pathology
• Intestinal Mucosa/metabolism
• Intestinal Mucosa/pathology
• Intestines/pathology
• Mice
• Mice, Transgenic
• Microbiota/physiology
• Receptors, Calcitriol/genetics
• Receptors, Calcitriol/metabolism
• Receptors, Calcitriol/physiology

• P30 DK042086 NIDDK NIH HHS
• R01 CA180087 NCI NIH HHS

• dendritic cell
• diet
• epithelial
• flavonoid
• inflammatory bowel disease

• BBS/E/J/00000153 Biotechnology and Biological Sciences Research Council
• BBS/E/J/0000A231 Biotechnology and Biological Sciences Research Council

• Dendritic cells
• Immunity
• Microbiota
• Omnivorous diet
• Vegan diet
• Vegetarian diet

• Animals
• B7-1 Antigen/genetics
• B7-2 Antigen/genetics
• Bifidobacterium/immunology
• Bifidobacterium/isolation & purification
• Cytokines/genetics
• Dendritic Cells/immunology
• Dendritic Cells/microbiology
• Diet
• Diet, Vegan
• Down-Regulation
• Feces/microbiology
• Gastrointestinal Microbiome/immunology
• Humans
• Immunomodulation
• Interleukin-10/genetics
• Interleukin-12/genetics
• Lactobacillus/immunology
• Lactobacillus/isolation & purification
• Mice
• Tumor Necrosis Factor-alpha/genetics
• Up-Regulation
• Vegetarians

Deficient mucosal innate immunity is a hallmark of infectious diarrhea, such as Salmonella typhimurium (S. typhimurium)-induced gastroenteritis. Here, we report that oral administration of a 4,4′-diaponeurosporene-producing Bacillus subtilis (B.s-Dia) could improve mice mucosal immunity, as showed by an increased resistance against S. typhimurium infection. Intragastric administration of B.s-Dia for 7 days could increase the secretion of CCL20 by intestinal epithelial cells (IECs) and then recruit more dendritic cells. Meanwhile, the number of CD8αα⁺ intraepithelial lymphocytes, which play a critical role in downregulating immune responses, was also reduced, probably as a consequence of the decrease of IEC-derived TGFβ. Further study showed that CD36 played a critical role in B.s-Dia-induced immune enhancement, as blocking CD36 signal with a specific antagonist, sulfo-N-succinimidyl oleate, led to the inability of B.s-Dia to enhance mucosal innate immunity.

• Bacillus subtilis
• C30 carotenoid
• CD36
• mucosal defense
• oral administration

The vertebrate gut symbiont Lactobacillus reuteri exhibits strain-specific adhesion and health-promoting properties. Here, we investigated the role of the mucus adhesins, CmbA and MUB, upon interaction of L. reuteri ATCC PTA 6475 and ATCC 53608 strains with human monocyte-derived dendritic cells (moDCs). We showed that mucus adhesins increased the capacity of L. reuteri strains to interact with moDCs and promoted phagocytosis. Our data also indicated that mucus adhesins mediate anti- and pro-inflammatory effects by the induction of interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-α), IL-1β, IL-6, and IL-12 cytokines. L. reuteri ATCC PTA 6475 and ATCC 53608 were exclusively able to induce moDC-mediated Th1 and Th17 immune responses. We further showed that purified MUB activates moDCs and induces Th1 polarized immune responses associated with increased IFNγ production. MUB appeared to mediate these effects via binding to C-type lectin receptors (CLRs), as shown using cell reporter assays. Blocking moDCs with antibodies against DC-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) or Dectin-2 did not affect the uptake of the MUB-expressing strain, but reduced the production of TNF-α and IL-6 by moDCs significantly, in line with the Th1 polarizing capacity of moDCs. The direct interaction between MUB and CLRs was further confirmed by atomic force spectroscopy. Taken together these data suggest that mucus adhesins expressed at the cell surface of L. reuteri strains may exert immunoregulatory effects in the gut through modulating the Th1-promoting capacity of DCs upon interaction with C-type lectins.

• C-type lectins
• DC-SIGN
• Dectin-2
• L. reuteri
• T-lymphocytes
• dendritic cells
• mucus adhesins
• probiotic

• allergic conjunctivitis
• conjunctival inflammation
• dry eye
• mucosal tolerance
• ocular mucosal immune system
• ocular surface

ST258-K. pneumoniae (ST258-KP) strains, the most widespread multidrug-resistant hospital-acquired pathogens, belong to at least two clades differing in a 215 Kb genomic region that includes the cluster of capsule genes. To investigate the effects of the different capsular phenotype on host-pathogen interactions, we studied representatives of ST258-KP clades, KKBO-1 and KK207-1, for their ability to activate monocytes and myeloid dendritic cells from human immune competent hosts. The two ST258-KP strains strongly induced the production of inflammatory cytokines. Significant differences between the strains were found in their ability to induce the production of IL-1β: KK207-1/clade I was much less effective than KKBO-1/clade II in inducing IL-1β production by monocytes and dendritic cells. The activation of NLRP3 inflammasome pathway by live cells and/or purified capsular polysaccharides was studied in monocytes and dendritic cells. We found that glibenclamide, a NLRP3 inhibitor, inhibits more than 90% of the production of mature IL-1β induced by KKBO1 and KK207-1. KK207-1 was always less efficient compared to KKBO-1 in: a) inducing NLRP3 and pro-IL-1β gene and protein expression; b) in inducing caspase-1 activation and pro-IL-1β cleavage. Capsular composition may play a role in the differential inflammatory response induced by the ST258-KP strains since capsular polysaccharides purified from bacterial cells affect NLRP3 and pro-IL-1β gene expression through p38MAPK- and NF-κB-mediated pathways. In each of these functions, capsular polysaccharides from KK207-1 were significantly less efficient compared to those purified from KKBO-1. On the whole, our data suggest that the change in capsular phenotype may help bacterial cells of clade I to partially escape innate immune recognition and IL-1β-mediated inflammation.

• Bacterial Proteins/metabolism
• Caspase 1/metabolism
• Dendritic Cells/immunology
• Dendritic Cells/metabolism
• Dendritic Cells/microbiology
• Endocytosis
• Gene Expression/drug effects
• Humans
• Inflammasomes/metabolism
• Interleukin-1beta/analysis
• Interleukin-1beta/genetics
• Interleukin-1beta/metabolism
• Interleukin-6/analysis
• Klebsiella Infections/enzymology
• Klebsiella Infections/immunology
• Klebsiella Infections/microbiology
• Klebsiella pneumoniae/enzymology
• Klebsiella pneumoniae/isolation & purification
• Monocytes/immunology
• Monocytes/metabolism
• Monocytes/microbiology
• NF-kappa B/metabolism
• NLR Family, Pyrin Domain-Containing 3 Protein/genetics
• NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
• Polysaccharides, Bacterial/isolation & purification
• Polysaccharides, Bacterial/pharmacology
• Signal Transduction/drug effects
• Tumor Necrosis Factor-alpha/analysis
• beta-Lactamases/metabolism
• p38 Mitogen-Activated Protein Kinases/metabolism

• Cassa di Risparmio di Firenze –CDRF- foundation

Probiotics, such as lactic acid bacteria (LAB) and Bacillus subtilis var. natto, have been shown to modulate immune responses. It is important to understand how probiotic bacteria impact intestinal epithelial cells (IECs), because IECs are the first line of defense at the mucosal surface barrier and their activities substantially affect the gut microenvironment and immunity. However, to date, their precise mechanism remains unknown due to a lack of analytical systems available for live animal models. Recently, we generated a conditional Ca²⁺ biosensor Yellow Cameleon (YC3.60) transgenic mouse line and established 5D (x, y, z, time, and Ca²⁺) intravital imaging systems of lymphoid tissues including those in Peyer’s patches and bone marrow. In the present study, we further advance our intravital imaging system for intestinal tracts to visualize IEC responses against orally administrated food compounds in real time. Using this system, heat-killed B. subtilis natto, a probiotic TTCC012 strain, is shown to directly induce Ca²⁺ signaling in IECs in mice housed under specific pathogen-free conditions. In contrast, this activation is not observed in the Lactococcus lactis strain C60; however, when we generate germ-free YC3.60 mice and observe the LAB stimulation of IECs in the absence of gut microbiota, C60 is capable of inducing Ca²⁺ signaling. This is the first study to successfully visualize the direct effect of probiotics on IECs in live animals. These data strongly suggest that probiotic strains stimulate IECs under physiological conditions and that their activity is affected by the microenvironment of the small intestine, such as commensal bacteria.

• Bacillus subtilis
• Ca2+ signaling
• Lactococcus
• germ-free mouse
• intestinal epithelial cell
• intravital imaging
• probiotic
• small intestine

• Animals
• Antigens, CD/genetics
• Antigens, CD/immunology
• Cell Differentiation
• Cell Lineage
• Cellular Microenvironment
• Dendritic Cells/immunology
• Dendritic Cells/physiology
• Integrin alpha Chains/genetics
• Integrin alpha Chains/immunology
• Integrin beta Chains/genetics
• Integrin beta Chains/immunology
• Integrin beta Chains/metabolism
• Intestines/cytology
• Intestines/immunology
• Mice
• T-Lymphocytes, Regulatory/physiology
• Toll-Like Receptors/immunology
• Toll-Like Receptors/metabolism
• Transforming Growth Factor beta/genetics
• Transforming Growth Factor beta/immunology
• Transforming Growth Factor beta/metabolism
• Tretinoin/metabolism

• G0802069 Medical Research Council
• G0901697 Medical Research Council
• R01 DK093695 NIDDK NIH HHS

In early‐life, the immature mucosal barrier allows contact between the gut microbiota and the developing immune system. Due to their strategic location and their ability to sample luminal antigen, dendritic cells (DC) play a central role in the interaction of microbes and immune cells in the gut. Here, we investigated how two bacteria associated with opposite immune profiles in children, that is, Lactobacillus (L.) reuteri and Staphylococcus (S.) aureus, influenced the differentiation of monocytes in vitro as well how the generated DC impacted T cell responses.

We exposed monocyte cultures to cell‐free supernatants (CFS) from these bacteria during their differentiation to DC.

The presence of L. reuteri‐CFS during DC differentiation resulted in DC with a more mature phenotype, in terms of up‐regulated surface markers (HLA‐DR, CD86, CD83, CCR7) and enhanced cytokine production (IL6, IL10, and IL23), but had a reduced phagocytic capacity compared with non‐treated monocyte‐derived DC (Mo‐DC). However, upon LPS activation, L. reuteri‐CFS‐generated DC displayed a more regulated phenotype than control Mo‐DC with notable reduction of cytokine responses both at mRNA and protein levels. In contrast, S. aureus‐CFS‐generated DC were more similar to control Mo‐DC both without and after LPS stimulation, but they were still able to induce responses in autologous T cells, in the absence of further T cell stimulation.

We show that bacterial signals during DC differentiation have a profound impact on DC function and possibly also for shaping the T cell pool.

• Cytokine
• Lactobacillus reuteri
• PCR array
• Staphylococcus aureus
• T cell
• dendritic cells
• monocytes

• Lactobacillus reuteri
• dendritic cells
• postbiotics
• probiotics
• retinoic acid

• Caesarean delivery
• Dysbiosis
• Gut microbiota
• Gut microbiota biomodulators
• Prebiotics
• Probiotics

• Bacteria/immunology
• Breast Feeding
• Cesarean Section
• Gastrointestinal Microbiome/immunology
• Gastrointestinal Tract/immunology
• Gastrointestinal Tract/microbiology
• Humans
• Infant
• Infant Formula/administration & dosage
• Parturition

One of the main tasks of the immune system is to discriminate and appropriately react to “danger” or “non-danger” signals. This is crucial in the gastrointestinal tract, where the immune system is confronted with a myriad of food antigens and symbiotic microflora that are in constant contact with the mucosa, in addition to any potential pathogens. This large number of antigens and commensal microflora, which are essential for providing vital nutrients, must be tolerated by the intestinal immune system to prevent aberrant inflammation. Hence, the balance between immune activation versus tolerance should be tightly regulated to maintain intestinal homeostasis and to prevent immune activation indiscriminately against all luminal antigens. Loss of this delicate equilibrium can lead to chronic activation of the intestinal immune response resulting in intestinal disorders, such as inflammatory bowel diseases (IBD). In order to maintain homeostasis, the immune system has evolved diverse regulatory strategies including additional non-immunological actors able to control the immune response. Accumulating evidence strongly indicates a bidirectional link between the two systems in which the brain modulates the immune response via the detection of circulating cytokines and via direct afferent input from sensory fibers and from enteric neurons. In the current review, we will highlight the most recent findings regarding the cross-talk between the nervous system and the mucosal immune system and will discuss the potential use of these neuronal circuits and neuromediators as novel therapeutic tools to reestablish immune tolerance and treat intestinal chronic inflammation.

• inflammatory bowel disease
• intestinal immune system
• neuropeptide
• oral tolerance
• parasympathetic system
• peptidergic pathway
• sympathetic system

Crohn’s disease (CD) is a systemic chronic inflammatory condition mainly characterized by discontinuous transmural pathology of the gastrointestinal tract and frequent extraintestinal manifestations with intermittent episodes of remission and relapse. Genome-wide association studies identified a number of risk loci that, catalyzed by environmental triggers, result in the loss of tolerance toward commensal bacteria based on dysregulated innate effector functions and antimicrobial defense, leading to exacerbated adaptive immune responses responsible for chronic immune-mediated tissue damage. In this review, we discuss the inter-related role of changes in the intestinal microbiota, epithelial barrier integrity, and immune cell functions on the pathogenesis of CD, describing the current approaches available to investigate the molecular mechanisms underlying the disease. Substantial effort has been dedicated to define disease-associated changes in the intestinal microbiota (dysbiosis) and to link pathobionts to the etiology of inflammatory bowel diseases. A cogent definition of dysbiosis is lacking, as well as an agreement of whether pathobionts or complex shifts in the microbiota trigger inflammation in the host. Among the rarely available animal models, SAMP/Yit and TNF^deltaARE mice are the best known displaying a transmural CD-like phenotype. New hypothesis-driven mouse models, e.g., epithelial-specific Caspase8^−/−, ATG16L1^−/−, and XBP1^−/− mice, validate pathway-focused function of specific CD-associated risk genes highlighting the role of Paneth cells in antimicrobial defense. To study the causal role of bacteria in initiating inflammation in the host, the use of germ-free mouse models is indispensable. Unraveling the interactions of genes, immune cells and microbes constitute a criterion for the development of safe, reliable, and effective treatment options for CD.

• Crohn’s disease
• IBD
• IEC
• Paneth cells
• TNF
• barrier dysfunction
• dysbiosis
• microbiota

• Autoimmunity
• B cells
• Celiac disease
• Gluten
• HLA
• T cells

Humans have coevolved with a complex community of bacterial species also referred to as the microbiome, which reciprocally provides critical contributions to human metabolism and immune system development. Gut microbiome composition differs significantly between individuals depending on host genetics, diet, and environmental factors. A dysregulation of the symbiotic nature of the intestinal host-microbial relationship and an aberrant and persistent immune response are the fundamental processes involved in inflammatory bowel diseases (IBD). Considering the essential role of T cells in IBD and the contributing role of the microbiome in shaping the immune response during the pathogenesis of IBD, this review focuses on the complex relationship, interplay, and communication between the gut microbiome and T cells, including their differentiation into different subsets of effector or regulatory cells.