Intestinal inflammation alters the antigen-specific immune response to a skin commensal.
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ABSTRACT:
SUBMITTER: Merana GR
PROVIDER: S-EPMC9248974 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Intestinal microbes induce homeostatic mucosal immune responses, but can also cause inappropriate immune activation in genetically susceptible hosts. Although immune responses to bacterial products have been studied extensively, little is known about how intestinal inflammation affects functions of commensal luminal microbes.Microarrays and real-time polymerase chain reaction were used to profile transcriptional changes in luminal bacteria from wild-type and IL-10(-/-) mice monoassociated with a nonpathogenic, murine isolate of Escherichia coli (NC101, which causes colitis in gnotobiotic IL-10(-/-) mice). Colonic inflammation and innate and adaptive immune responses were measured in wild-type and IL-10(-/-) mice monoassociated with mutant NC101 that lack selected, up-regulated genes, and in IL-10(-/-) mice that were colonized with a combination of mutant and parental NC101. We measured intracellular survival of bacteria within primary macrophages from mice and resulting production of tumor necrosis factor.Bacteria from IL-10(-/-) mice with colitis had significant up-regulation of the stress-response regulon, including the small heat shock proteins IbpA and IbpB that protect E coli from oxidative stress, compared to healthy, wild-type controls. In IL-10(-/-) mice, expression of ibpAB reduced histologic signs of colon inflammation, secretion of interleukin-12/23p40 in colonic explant cultures, serologic reactivity to NC101 antigens, and secretion of interferon-gamma by stimulated mesenteric lymph node cells. Infection of primary macrophages by bacteria that express ibpAB was associated with decreased intracellular survival and reduced secretion of tumor necrosis factor.Chronic intestinal inflammation causes functional alterations in gene expression in commensal gut bacterium (E coli NC101). Further studies of these expression patterns might identify therapeutic targets for patients with inflammatory bowel diseases.
| S-EPMC3624969 | biostudies-literature
Project description:Background/aimsExtracellular vesicles (EVs) are secreted from various types of cells and have specific functions related to their origin. EVs are observed in the small intestinal lamina propria (lpEVs), but their function remains unclear. This study aimed to investigate the role of lpEVs.MethodsLpEVs were isolated from antigen (ovalbumin [OVA])-fed mice (lpEVs/OVA), and administrated to the naïve mice for 5 days before induction of lung inflammation. Afterwards, the mice were sensitized and challenged with OVA to evaluate the role of lpEVs/OVA in the regulation of immune tolerance.ResultsThe isolated lpEVs/OVA were sphere-shaped, bi-layered vesicles of approximately 50 to 100 nm in size. The vesicles expressed CD81, A33 antigen, and major histocompatibility complex (MHC) class II on the surface. When administrated to naïve mice, the lpEVs/OVA migrated to the spleen. Intraperitoneal lpEVs/OVA administration to naïve mice decreased the immune response against sensitized antigen in a CD4+FoxP3+T cell-dependent manner.ConclusionEVs are actively secreted from small intestinal epithelial cells to deliver information about orally administered antigens to immune cells, which will facilitate the modulation of the immune response by acting as an intercellular communicasome.
| S-EPMC8747917 | biostudies-literature
Project description:Under steady-state conditions, the immune system is poised to sense and respond to the microbiota. As such, immunity to the microbiota, including T cell responses, is expected to precede any inflammatory trigger. How this pool of preformed microbiota-specific T cells contributes to tissue pathologies remains unclear. Here, using an experimental model of psoriasis, we show that recall responses to commensal skin fungi can significantly aggravate tissue inflammation. Enhanced pathology caused by fungi preexposure depends on Th17 responses and neutrophil extracellular traps and recapitulates features of the transcriptional landscape of human lesional psoriatic skin. Together, our results propose that recall responses directed to skin fungi can directly promote skin inflammation and that exploration of tissue inflammation should be assessed in the context of recall responses to the microbiota.
| S-EPMC7368261 | biostudies-literature
Project description:The skin microbiome can both trigger beneficial immune stimulation and pose a potential infection threat. Previous studies have shown that colonization of mouse skin with the model human skin commensal Staphylococcus epidermidis is protective against subsequent excisional wound or pathogen challenge. However, less is known about concurrent skin damage and exposure to commensal microbes, despite growing interest in interventional probiotic therapy. Here, we address this open question by applying commensal skin bacteria at a high dose to abraded skin. While depletion of the skin microbiome via antibiotics delayed repair from damage, application of commensals-- including the mouse commensal Staphylococcus xylosus, three distinct isolates of S. epidermidis, and all other tested human skin commensals-- also significantly delayed barrier repair. Increased inflammation was observed within four hours of S. epidermidis exposure and persisted through day four, at which point the skin displayed a chronic-wound-like inflammatory state with increased neutrophil infiltration, increased fibroblast activity, and decreased monocyte differentiation. Transcriptomic analysis suggested that the prolonged upregulation of early canonical proliferative pathways inhibited the progression of barrier repair. These results highlight the nuanced role of members of the skin microbiome in modulating barrier integrity and indicate the need for caution in their development as probiotics.
| S-EPMC10723327 | biostudies-literature
Project description:The mammalian intestine is home to a dense community of bacteria and its associated bacteriophage (phage). Virtually nothing is known about how phages impact the establishment and maintenance of resident bacterial communities in the intestine. Here, we examine the phages harbored by Enterococcus faecalis, a commensal of the human intestine. We show that E. faecalis strain V583 produces a composite phage (?V1/7) derived from two distinct chromosomally encoded prophage elements. One prophage, prophage 1 (?V1), encodes the structural genes necessary for phage particle production. Another prophage, prophage 7 (?V7), is required for phage infection of susceptible host bacteria. Production of ?V1/7 is controlled, in part, by nutrient availability, because ?V1/7 particle numbers are elevated by free amino acids in culture and during growth in the mouse intestine. ?V1/7 confers an advantage to E. faecalis V583 during competition with other E. faecalis strains in vitro and in vivo. Thus, we propose that E. faecalis V583 uses phage particles to establish and maintain dominance of its intestinal niche in the presence of closely related competing strains. Our findings indicate that bacteriophages can impact the dynamics of bacterial colonization in the mammalian intestinal ecosystem.
| S-EPMC3491505 | biostudies-other
Project description:The human nasopharynx contains a stable microbial ecosystem of commensal and potentially pathogenic bacteria, which can elicit protective primary and secondary immune responses. Experimental intranasal infection of human adults with the commensal Neisseria lactamica produced safe, sustained pharyngeal colonization. This has potential utility as a vehicle for sustained release of antigen to the human mucosa, but commensals in general are thought to be immunologically tolerated. Here, we show that engineered N. lactamica, chromosomally transformed to express a heterologous vaccine antigen, safely induces systemic, antigen-specific immune responses during carriage in humans. When the N. lactamica expressing the meningococcal antigen Neisseria Adhesin A (NadA) was inoculated intranasally into human volunteers, all colonized participants carried the bacteria asymptomatically for at least 28 days, with most (86%) still carrying the bacteria at 90 days. Compared to an otherwise isogenic but phenotypically wild-type strain, colonization with NadA-expressing N. lactamica generated NadA-specific immunoglobulin G (IgG)- and IgA-secreting plasma cells within 14 days of colonization and NadA-specific IgG memory B cells within 28 days of colonization. NadA-specific IgG memory B cells were detected in peripheral blood of colonized participants for at least 90 days. Over the same period, there was seroconversion against NadA and generation of serum bactericidal antibody activity against a NadA-expressing meningococcus. The controlled infection was safe, and there was no transmission to adult bedroom sharers during the 90-day period. Genetically modified N. lactamica could therefore be used to generate beneficial immune responses to heterologous antigens during sustained pharyngeal carriage.
| S-EPMC7615050 | biostudies-literature
Project description:Psoriasis is a chronic inflammatory skin disease in which Th17 cells play a crucial role. Since indigenous gut microbiota influences the development and reactivity of immune cells, we analyzed the link among microbiota, T cells and the formation of psoriatic lesions in the imiquimod-induced murine model of psoriasis. To explore the role of microbiota, we induced skin inflammation in germ-free (GF), broad-spectrum antibiotic (ATB)-treated or conventional (CV) BALB/c and C57BL/6 mice. We found that both mice reared in GF conditions for several generations and CV mice treated with ATB were more resistant to imiquimod-induced skin inflammation than CV mice. The ATB treatment dramatically changed the diversity of gut bacteria, which remained stable after subsequent imiquimod application; ATB treatment resulted in a substantial increase in the order Lactobacillales and a significant decrease in Coriobacteriales and Clostridiales. Moreover, as compared to CV mice, imiquimod induced a lower degree of local and systemic Th17 activation in both GF and ATB-treated mice. These findings suggest that gut microbiota control imiquimod-induced skin inflammation by altering the T cell response.
| S-EPMC4951142 | biostudies-literature
Project description:Several genetic variants in the mitochondrial genome (mtDNA), including ancient polymorphisms, are associated with chronic inflammatory conditions, but investigating the functional consequences of such mtDNA polymorphisms in humans is challenging due to the influence of many other polymorphisms in both mtDNA and the nuclear genome (nDNA). Here, using the conplastic mouse strain B6-mtFVB, we show that in mice, a maternally inherited natural mutation (m.7778G > T) in the mitochondrially encoded gene ATP synthase 8 (mt-Atp8) of complex V impacts on the cellular metabolic profile and effector functions of CD4+ T cells and induces mild changes in oxidative phosphorylation (OXPHOS) complex activities. These changes culminated in significantly lower disease susceptibility in two models of inflammatory skin disease. Our findings provide experimental evidence that a natural variation in mtDNA influences chronic inflammatory conditions through alterations in cellular metabolism and the systemic metabolic profile without causing major dysfunction in the OXPHOS system.
| S-EPMC7863969 | biostudies-literature
Project description:Under steady state conditions, the immune system is poised to sense and respond to the microbiota. As such, immunity to the microbiota, including T cell responses, is expected to precede any inflammatory trigger. How this pool of preformed microbiota-specific T cells contributes to tissue pathologies remains unclear. Here, using an experimental model of psoriasis, we show that recall responses to commensal skin fungi can significantly aggravate tissue inflammation. Enhanced pathology caused by fungi pre-exposure depends on Th17 responses and neutrophil extracellular traps and recapitulates features of the transcriptional landscape of human lesional psoriatic skin. Together, our results propose that recall responses directed to skin fungi can directly promote skin inflammation and that exploration of tissue inflammation should be assessed in the context of recall responses to the microbiota.
2020-09-22 | GSE144850 | GEO
Project description:BackgroundSchizophrenia is characterized by several core behavioral features, in which the gastrointestinal symptoms are frequently reported. Maternal immune activation (MIA) has been developed in a rodent model to study neurodevelopmental disorders such as schizophrenia. However, the changes in the gut environment of MIA rats remain largely unknown.Methods10 mg/kg of polyinosinic:polycytidylic acid (Poly I:C) on gestational day 9 was intravenously administered to rats to induce MIA in order to assess changes in behavior, the intestinal barrier and microbiota in offspring.ResultsMaternal immune activation offspring shown increased anxiety as indicated by reduced exploration of central area in open field test and decreased exploration of open arms in elevated plus test. Cognitive impairment of MIA offspring was confirmed by reduced exploration of novel arm in Y maze test and deficiency of PPI. Intestinal muscle thickness became thinner and some specific microbial anomalies previously identified clinically were observed in MIA offspring. In addition, an increase of inflammatory responses was found in the gut of MIA offspring.ConclusionsMaternal immune activation alters behavior, intestinal integrity, gut microbiota and the gut inflammation in adult offspring.
| S-EPMC8119836 | biostudies-literature