scholarly journals Segmented Filamentous Bacteria Are Potent Stimuli of a Physiologically Normal State of the Murine Gut Mucosal Immune System

1999 ◽  
Vol 67 (4) ◽  
pp. 1992-2000 ◽  
Author(s):  
Gwen L. Talham ◽  
Han-Qing Jiang ◽  
Nicolaas A. Bos ◽  
John J. Cebra
Keyword(s):  
T Cells ◽  
Immune System ◽  
Immunoglobulin A ◽  
Mucosal Immune System ◽  
Filamentous Bacteria ◽  
Mesenteric Lymph Nodes ◽  
Segmented Filamentous Bacteria ◽  
Iga Antibody ◽  
Autochthonous Bacteria ◽  
Iga Production

ABSTRACT Segmented filamentous bacteria (SFB) are autochthonous bacteria inhabiting the intestinal tracts of many species, including humans. We studied the effect of SFB on the mucosal immune system by monoassociating formerly germfree C3H/HeN mice with SFB. At various time points during 190 days of colonization, fragment cultures of small intestine and Peyer’s patches (PP) were analyzed for total immunoglobulin A (IgA) and SFB-specific IgA production. Also, phenotypic changes indicating germinal center reactions (GCRs) and the activation of CD4+ T cells in PP were determined by using fluorescence-activated cell sorter analyses. A second group of SFB-monoassociated mice was colonized with a gram-negative commensal,Morganella morganii, to determine if the mucosal immune system was again stimulated and to evaluate the effect of prior colonization with SFB on the ability of M. morganii to translocate to the spleen and mesenteric lymph nodes. We found that SFB stimulated GCRs in PP from day 6 after monoassociation, that GCRs only gradually waned over the entire length of colonization, that natural IgA production was increased to levels 24 to 63% of that of conventionally reared mice, and that SFB-specific IgA was produced but accounted for less than 1.4% of total IgA. Also, the proportion of CD4+, CD45RBlow T cells, indicative of activated cells, gradually increased in the PP to the level found in conventionally reared mice. Secondary colonization with M. morganii was able to stimulate GCRs anew, leading to a specific IgA antibody response. Previous stimulation of mucosal immunity by SFB did not prevent the translocation of M. morganii in the double-colonized mice. Our findings generally indicate that SFB are one of the single most potent microbial stimuli of the gut mucosal immune system.

Interactions between gut-associated lymphoid tissue and colonization levels of indigenous, segmented, filamentous bacteria in the small intestine of mice

1998 ◽  
Vol 44 (12) ◽  
pp. 1177-1182 ◽  
Author(s):  
J Snel ◽  
C C Hermsen ◽  
H J Smits ◽  
N A Bos ◽  
WMC Eling ◽  
...  
Keyword(s):  
Small Intestine ◽  
Immune System ◽  
Lymphoid Tissue ◽  
Immune Reaction ◽  
Mucosal Immune System ◽  
Filamentous Bacteria ◽  
Segmented Filamentous Bacteria ◽  
Swiss Mice ◽  
Age Dependent ◽  
Old Mice

Unlike most other indigenous bacteria, segmented filamentous bacteria (SFB) are potent activators of the mucosal immune system. SFB are strongly anchored to the epithelial cells of the small intestine where they have a preference for mucosal lymphoid epithelium. Since SFB are only present in high numbers shortly after weaning, it was investigated whether an SFB-induced immune reaction results in the removal of these bacteria from the small intestine. A correlation was found between age and colonization levels in the small intestines of SFB monoassociated Swiss mice. Five-week-old athymic BALB/c (nu/nu) mice showed lower colonization levels than their heterozygous littermates, but the opposite was found at the age of 12 weeks. However, SFB inoculation of germfree Swiss mice resulted in higher colonization levels in 5-week-old mice when compared with 4-month-old mice. We conclude that SFB colonization levels in the small intestine are likely influenced by the activity of the mucosal immune system. However, an additional age-dependent factor that modulates SFB colonization levels cannot be excluded.Key words: segmented filamentous bacteria, small intestine, gut-associated lymphoid tissue.

scholarly journals Differential Roles of Segmented Filamentous Bacteria and Clostridia in Development of the Intestinal Immune System

1999 ◽  
Vol 67 (7) ◽  
pp. 3504-3511 ◽  
Author(s):  
Yoshinori Umesaki ◽  
Hiromi Setoyama ◽  
Satoshi Matsumoto ◽  
Akemi Imaoka ◽  
Kikuji Itoh
Keyword(s):  
Small Intestine ◽  
Immune System ◽  
Large Intestine ◽  
Immunoglobulin A ◽  
Cell Receptor ◽  
Intraepithelial Lymphocytes ◽  
Filamentous Bacteria ◽  
Segmented Filamentous Bacteria ◽  
Intestinal Immune System ◽  
Gnotobiotic Mice

ABSTRACT The presence of microflora in the digestive tract promotes the development of the intestinal immune system. In this study, to evaluate the roles of two types of indigenous microbe, segmented filamentous bacteria (SFB) and clostridia, whose habitats are the small and large intestines, respectively, in this immunological development, we analyzed three kinds of gnotobiotic mice contaminated with SFB, clostridia, and both SFB and clostridia, respectively, in comparison with germfree (GF) or conventionalized (Cvd) mice associated with specific-pathogen-free flora. In the small intestine, the number of αβ T-cell receptor-bearing intraepithelial lymphocytes (αβIEL) increased in SFB-associated mice (SFB-mice) but not in clostridium-associated mice (Clost-mice). There was no great difference in Vβ usage among GF mice, Cvd mice, and these gnotobiotic mice, although the association with SFB decreased the proportion of Vβ6+ cells in CD8β− subsets to some extent, compared to that in GF mice. The expression of major histocompatibility complex class II molecules on the epithelial cells was observed in SFB-mice but not in Clost-mice. On the other hand, in the large intestine, the ratio of the number of CD4−CD8+ cells to that of CD4+ CD8−cells in αβIEL increased in Clost-mice but not in SFB-mice. On association with both SFB and clostridia, the numbers and phenotypes of IEL in the small and large intestines changed to become similar to those in Cvd mice. In particular, the ratio of the number of CD8αβ+ cells to that of CD8αα+ cells in αβIEL, unusually elevated in the small intestines of SFB-mice, decreased to the level in Cvd mice on contamination with both SFB and clostridia. The number of immunoglobulin A (IgA)-producing cells in the lamina propria was more elevated in SFB-mice than in Clost-mice, not only in the ileum but also in the colon. The number of IgA-producing cells in the colons of Clost-mice was a little increased compared to that in GF mice. Taken together, SFB and clostridia promoted the development of both IEL and IgA-producing cells in the small intestine and that of only IEL in the large intestine, respectively, suggesting the occurrence of compartmentalization of the immunological responses to the indigenous bacteria between the small and large intestines.

scholarly journals Apathogenic, intestinal, segmented, filamentous bacteria stimulate the mucosal immune system of mice.

1993 ◽  
Vol 61 (1) ◽  
pp. 303-306 ◽  
Author(s):  
H L Klaasen ◽  
P J Van der Heijden ◽  
W Stok ◽  
F G Poelma ◽  
J P Koopman ◽  
...  
Keyword(s):  
Immune System ◽  
Mucosal Immune System ◽  
Filamentous Bacteria ◽  
Segmented Filamentous Bacteria

scholarly journals Transmission Electron Microscopic Demonstration of Phagocytosis and Intracellular Processing of Segmented Filamentous Bacteria by Intestinal Epithelial Cells of the Chick Ileum

2000 ◽  
Vol 68 (11) ◽  
pp. 6496-6504 ◽  
Author(s):  
Koh-En Yamauchi ◽  
Johannes Snel
Keyword(s):  
Immune System ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Mucosal Immune System ◽  
Host Cells ◽  
Intestinal Lumen ◽  
Intestinal Epithelial ◽  
Filamentous Bacteria ◽  
Segmented Filamentous Bacteria ◽  
Transmission Electron

ABSTRACT Segmented filamentous bacteria (SFB) are autochthonous bacteria colonizing the ileum of many young animals by attaching to intestinal epithelial cells. These nonpathogenic bacteria strongly stimulate the mucosal immune system and induce intestinal epithelial cells to express major histocompatibility complex class II molecules. We tried to discover whether SFB are phagocytized and intracellularly processed by the host cells, which is indicative of antigen processing. The middle part of the ileum was extracted from 10- and 20-day-old broiler chicks (Gallus gallus domesticus). Samples were processed and examined by scanning and transmission electron microscopy (SEM and TEM, respectively). In SEM, no, few, medium, and dense SFB colonization levels were classified. In TEM of cells from animals with medium or dense SFB colonization levels, we could observe extracellular particles ranging from those only indenting the cell membrane to particles found in the cytoplasmatic area beyond the terminal web. These particles had a structural similarity with SFB that were floating freely in the intestinal lumen. Furthermore, we observed unlacing of the membrane and septum surrounding the extracellular particles and their incorporation into host cytoplasmatic components, which strongly suggests that these particles are phagocytized and intracellularly processed SFB. This conclusion is supported by TEM analysis of samples with no or few SFB, in which we failed to find these characteristic morphologies. The phagocytosis process described here could be an important trigger for the stimulating effect of SFB on the mucosal immune system.

scholarly journals Functional Foxp3+ CD4+ CD25(Bright+) “Natural” Regulatory T Cells Are Abundant in Rabbit Conjunctiva and Suppress Virus-Specific CD4+ and CD8+ Effector T Cells during Ocular Herpes Infection

2007 ◽  
Vol 81 (14) ◽  
pp. 7647-7661 ◽  
Author(s):  
Anthony B. Nesburn ◽  
Ilham Bettahi ◽  
Gargi Dasgupta ◽  
Alami Aziz Chentoufi ◽  
Xiuli Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Peripheral Blood ◽  
Mucosal Immune System ◽  
Ocular Infection ◽  
Bulbar Conjunctiva ◽  
Herpes Infection ◽  
Ocular Herpes ◽  
Hsv 1

ABSTRACT We studied the phenotype and distribution of “naturally” occurring CD4+ CD25+ T regulatory cells (CD4+ CD25+ nTreg cells) resident in rabbit conjunctiva, the main T-cell inductive site of the ocular mucosal immune system, and we investigated their suppressive capacities using herpes simplex virus type 1 (HSV-1)-specific effector T (Teff) cells induced during ocular infection. The expression of CD4, CD25, CTLA4, GITR, and Foxp3 was examined by reverse transcription-PCR, Western blotting, and fluorescence-activated cell sorter analysis in CD45+ pan-leukocytes isolated from conjunctiva, spleen, and peripheral blood monocyte cells (PBMC) of HSV-1-infected and uninfected rabbits. Normal conjunctiva showed a higher frequency of CD4+ CD25(Bright+) T cells than did spleen and PBMC. These cells expressed high levels of Foxp3, GITR, and CTLA4 molecules. CD4+ CD25(Bright+) T cells were localized continuously along the upper and lower palpebral and bulbar conjunctiva, throughout the epithelium and substantia propria. Conjunctiva-derived CD4+ CD25(Bright+) T cells, but not CD4+ CD25(low) T cells, efficiently suppressed HSV-specific CD4+ and CD8+ Teff cells. The CD4+ CD25(Bright+) T-cell-mediated suppression was effective on both peripheral blood and conjunctiva infiltrating Teff cells and was cell-cell contact dependent but independent of interleukin-10 and transforming growth factor β. Interestingly, during an ocular herpes infection, there was a selective increase in the frequency and suppressive capacity of Foxp3+ CD4+ CD25(Bright+) T cells in conjunctiva but not in the spleen or in peripheral blood. Altogether, these results provide the first evidence that functional Foxp3+ CD4+ CD25(Bright+) Treg cells accumulate in the conjunctiva. It remains to be determined whether conjunctiva CD4+ CD25+ nTreg cells affect the topical/mucosal delivery of subunit vaccines that stimulate the ocular mucosal immune system.

scholarly journals Genome sequence of segmented filamentous bacteria present in the human intestine

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Hans Jonsson ◽  
Luisa W. Hugerth ◽  
John Sundh ◽  
Eva Lundin ◽  
Anders F. Andersson
Keyword(s):  
Amino Acid Identity ◽  
Phylogenomic Analysis ◽  
Host Immune System ◽  
Filamentous Bacteria ◽  
Segmented Filamentous Bacteria ◽  
Average Amino Acid Identity ◽  
Specific Manner ◽  
Iga Production ◽  
T Cell Maturation ◽  
Human Specific

AbstractSegmented filamentous bacteria (SFB) are unique immune modulatory bacteria colonizing the small intestine of a variety of animals in a host-specific manner. SFB exhibit filamentous growth and attach to the host’s intestinal epithelium, offering a physical route of interaction. SFB affect functions of the host immune system, among them IgA production and T-cell maturation. Until now, no human-specific SFB genome has been reported. Here, we report the metagenomic reconstruction of an SFB genome from a human ileostomy sample. Phylogenomic analysis clusters the genome with SFB genomes from mouse, rat and turkey, but the genome is genetically distinct, displaying 65–71% average amino acid identity to the others. By screening human faecal metagenomic datasets, we identified individuals carrying sequences identical to the new SFB genome. We thus conclude that a unique SFB variant exists in humans and foresee a renewed interest in the elucidation of SFB functionality in this environment.

scholarly journals Whole tissue homogenization preferable to mucosal scraping in determining the temporal profile of segmented filamentous bacteria in the ileum of weanling rats

2021 ◽  
Vol 3 (3) ◽  
Author(s):  
Linda A. Oemcke ◽  
Rachel C. Anderson ◽  
Jasna Rakonjac ◽  
Warren C. McNabb ◽  
Nicole C. Roy
Keyword(s):  
Immunoglobulin A ◽  
Interleukin 17 ◽  
Filamentous Bacteria ◽  
Sprague Dawley ◽  
Suitable Alternative ◽  
Segmented Filamentous Bacteria ◽  
Sprague Dawley Rats ◽  
Weanling Rats ◽  
Ileal Tissue ◽  
Mucosal Scraping

Segmented filamentous bacteria (SFB) are thought to play a role in small intestine immunological maturation. Studies in weanling mice have shown a positive correlation between ileal SFB abundance and plasma and faecal interleukin 17 (IL-17) and immunoglobulin A (IgA) concentrations. Although the first observation of SFB presence was reported in rats, most studies use mice. The size of the mouse ileum is a limitation whereas the rat could be a suitable alternative for sufficient samples. Changes in SFB abundance over time in rats were hypothesized to follow the pattern reported in mice and infants. We characterized the profile of SFB colonization in the ileum tissue and contents and its correlation with two immune markers of gastrointestinal tract (GIT) maturation. We also compared two published ileum collection techniques to determine which yields data on SFB abundance with least variability. Whole ileal tissue and ileal mucosal scrapings were collected from 20- to 32-day-old Sprague-Dawley rats. SFB abundance was quantified from proximal, middle and distal ileal tissues, contents and faeces by quantitative PCR using SFB-specific primers. Antibody-specific ELISAs were used to determine IL-17 and IgA concentrations. Significant differences in SFB abundance were observed from whole and scraped tissues peaking at day 22. Variability in whole ileum data was less, favouring it as a better collection technique. A similar pattern of SFB abundance was observed in ileum contents and faeces peaking at day 24, suggesting faeces can be a proxy for ileal SFB abundance. SFB abundance at day 26 was higher in females than males across all samples. There were significant differences in IgA concentration between days 20, 30 and 32 and none in IL-17 concentration, which was different from reports in mice and infants.

scholarly journals Modified Immunogenicity of a Mucosally Administered Antigen

2001 ◽  
Vol 8 (3) ◽  
pp. 540-544 ◽  
Author(s):  
Richard L. Gregory
Keyword(s):  
Immune System ◽  
Immunoglobulin A ◽  
Human Saliva ◽  
Mucosal Immune System ◽  
Antigenic Determinants ◽  
Enzyme Linked Immunosorbent Assay ◽  
Igg Antibodies ◽  
Serum Samples ◽  
Naturally Occurring ◽  
The Common

ABSTRACT Streptococcus mutans is present in the saliva of most individuals and is modified by salivary components bound to the cells. These saliva-bound S. mutans are swallowed, exposed to high levels of acidity in the stomach, and presented to the common mucosal immune system. Much effort has been directed to identifying the specific S. mutans antigens that the mucosal immune responses are directed against. However, little is known about the host-altered antigenic determinants that the mucosal immune system recognizes. The immunogenicity of gastrically intubated untreatedS. mutans cells, cells coated with whole human saliva, cells treated with HCl (pH 2.0), and saliva-coated and acid-treated cells in mice was investigated. Saliva and serum samples were assayed by enzyme linked immunosorbent assay for immunoglobulin A (IgA) and IgG antibodies, respectively, against the untreated or treated S. mutans cells. In general, the levels of salivary IgA and serum IgG antibodies to the antigen against which the mice were immunized were significantly higher (P ≤ 0.05). In addition, human saliva and serum samples from 12 subjects were assayed for naturally occurring antibody against the untreated or treated S. mutans cells. In every case, significantly higher reactivity was directed against the saliva-coated and acid-treated cells followed by the saliva-coated S. mutans. These results provide evidence for the altered immunogenicity of swallowed S. mutans in humans by coating native S. mutans antigens with salivary components and/or denaturing surface S. mutans antigens in the acidic environment of the stomach, which would lead to an immune response to modified S. mutans determinants and not to native S. mutans antigens.

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