Segmented filamentous bacteria are potent stimuli of a physiologically normal state of the murine gut mucosal immune system - PubMed (original) (raw)
Segmented filamentous bacteria are potent stimuli of a physiologically normal state of the murine gut mucosal immune system
G L Talham et al. Infect Immun. 1999 Apr.
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.
Figures
FIG. 1
In order to assess the progress of germinal center reactions and activation of T cells in PP, cell suspensions from PP of three to five mice were analyzed by FACS analysis at various times following the colonization of formerly GF mice with SFB. These analyses were compared to those of PP from GF and conventionally reared (CNV) mice. Cells were stained with a germinal center marker, PNA, conjugated to FLU or FLU-labeled goat anti-mouse IgA, respectively, and then both were counterstained with PE-conjugated anti-kappa chain to monitor the development of germinal center reactions. Cells were also stained with the CD4 T-cell activation marker CD45RB, conjugated to FLU and counterstained with PE-conjugated anti-CD4 to monitor T-cell activation.
FIG. 2
Production of total IgA in supernatant of organ fragment cultures of PP and small intestine of GF, conventionally reared (CONV), and SFB-monoassociated C3H/HeN mice at various time points. RIA was used to detect IgA. Data are means ± standard errors of the mean. SI, small intestine; D, duodenum; J, jejunum; I, ileum. The number of fragment cultures per tissue per time point ranged from 4 to 14.
FIG. 3
Production of total IgA in supernatant of organ fragment cultures of PP and small intestine (SI) of GF mice, conventionally reared (CNV) C3H/HeN mice, and C3H/HeN mice that had been monoassociated with SFB and then double associated (at day 113) with M. morganii. RIA was used to detect IgA. Data are means ± standard errors of the mean. The number of fragment cultures per tissue per time point ranged from 6 to 19.
FIG. 4
Production of anti-SFB specific IgA in supernatant of organ fragment cultures of PP and small intestine of GF, conventionally reared (CONV), and SFB-monoassociated C3H/HeN mice at various time points. RIA was used to detect IgA. Data are means ± standard errors of the mean. SI, small intestine; D, duodenum; J, jejunum; I, ileum. The number of fragment cultures per tissue per time point ranged from 4 to 14.
FIG. 5
Production of anti-SFB specific IgA in supernatant of organ fragment cultures of PP and small intestine (SI) of GF mice, conventionally reared (CNV) C3H/HeN mice, and C3H/HeN mice that had been monoassociated with SFB and then double associated (at day 113) with M. morganii. RIA was used to detect IgA. Data are means ± standard errors of the mean. The number of fragment cultures per tissue per time point ranged from 6 to 19.
FIG. 6
Production of anti-M. morganii specific IgA in supernatant of organ fragment cultures of PP and small intestine (SI) of GF mice, conventionally reared C3H/HeN mice, and C3H/HeN mice that had been monoassociated with SFB and then double associated (at day 113) with M. morganii. RIA was used to detect IgA. Data are means ± standard errors of the mean. Four fragment cultures were done per tissue per time point.
Similar articles
- Use of Peyer's patch and lymph node fragment cultures to compare local immune responses to Morganella morganii.
Logan AC, Chow KP, George A, Weinstein PD, Cebra JJ. Logan AC, et al. Infect Immun. 1991 Mar;59(3):1024-31. doi: 10.1128/iai.59.3.1024-1031.1991. Infect Immun. 1991. PMID: 1825484 Free PMC article. - Commensal enteric bacteria engender a self-limiting humoral mucosal immune response while permanently colonizing the gut.
Shroff KE, Meslin K, Cebra JJ. Shroff KE, et al. Infect Immun. 1995 Oct;63(10):3904-13. doi: 10.1128/iai.63.10.3904-3913.1995. Infect Immun. 1995. PMID: 7558298 Free PMC article. - Differential roles of segmented filamentous bacteria and clostridia in development of the intestinal immune system.
Umesaki Y, Setoyama H, Matsumoto S, Imaoka A, Itoh K. Umesaki Y, et al. Infect Immun. 1999 Jul;67(7):3504-11. doi: 10.1128/IAI.67.7.3504-3511.1999. Infect Immun. 1999. PMID: 10377132 Free PMC article. - Mucosal immunoregulation: environmental lipopolysaccharide and GALT T lymphocytes regulate the IgA response.
McGhee JR, Michalek SM, Kiyono H, Eldridge JH, Colwell DE, Williamson SI, Wannemuehler MJ, Jirillo E, Mosteller LM, Spalding DM, et al. McGhee JR, et al. Microbiol Immunol. 1984;28(3):261-80. doi: 10.1111/j.1348-0421.1984.tb00679.x. Microbiol Immunol. 1984. PMID: 6234450 Review. - IgA adaptation to the presence of commensal bacteria in the intestine.
Macpherson AJ. Macpherson AJ. Curr Top Microbiol Immunol. 2006;308:117-36. doi: 10.1007/3-540-30657-9_5. Curr Top Microbiol Immunol. 2006. PMID: 16922088 Review.
Cited by
- Gut-Brain Axis: Role of Microbiome, Metabolomics, Hormones, and Stress in Mental Health Disorders.
Verma A, Inslicht SS, Bhargava A. Verma A, et al. Cells. 2024 Aug 27;13(17):1436. doi: 10.3390/cells13171436. Cells. 2024. PMID: 39273008 Free PMC article. Review. - Gut commensals require Peyer's patches to induce protective systemic IgA responses.
Harris JR, Zoccoli-Rodriguez V, Delaney MS, Cruz TN, Gaudette BT, Wilmore JR. Harris JR, et al. Res Sq [Preprint]. 2024 May 13:rs.3.rs-4220532. doi: 10.21203/rs.3.rs-4220532/v1. Res Sq. 2024. PMID: 38798510 Free PMC article. Preprint. - Critical role of the gut microbiota in immune responses and cancer immunotherapy.
Li Z, Xiong W, Liang Z, Wang J, Zeng Z, Kołat D, Li X, Zhou D, Xu X, Zhao L. Li Z, et al. J Hematol Oncol. 2024 May 14;17(1):33. doi: 10.1186/s13045-024-01541-w. J Hematol Oncol. 2024. PMID: 38745196 Free PMC article. Review. - Multidirectional associations between the gut microbiota and Parkinson's disease, updated information from the perspectives of humoral pathway, cellular immune pathway and neuronal pathway.
Jia X, Chen Q, Zhang Y, Asakawa T. Jia X, et al. Front Cell Infect Microbiol. 2023 Dec 15;13:1296713. doi: 10.3389/fcimb.2023.1296713. eCollection 2023. Front Cell Infect Microbiol. 2023. PMID: 38173790 Free PMC article. Review. - α-Glucosidase inhibitors boost gut immunity by inducing IgA responses in Peyer's patches.
Hattori-Muroi K, Naganawa-Asaoka H, Kabumoto Y, Tsukamoto K, Fujisaki Y, Fujimura Y, Komiyama S, Kinashi Y, Kato M, Sato S, Takahashi D, Hase K. Hattori-Muroi K, et al. Front Immunol. 2023 Nov 1;14:1277637. doi: 10.3389/fimmu.2023.1277637. eCollection 2023. Front Immunol. 2023. PMID: 38022673 Free PMC article.
References
- Bos N A, Bun J C A M, Popma S H, Cebra E R, Deenen G J, van der Cammen M J, Kroese F G M, Cebra J J. Monoclonal immunoglobulin A derived from peritoneal B cells is encoded by both germ line and somatically mutated VH genes and is reactive with commensal bacteria. Infect Immun. 1996;64:616–623. - PMC - PubMed
- Bos N A, Meeuwesen C G, Wostmann B S, Pleasants J R, Brenner R. The influence of exogenous antigenic stimulation on the specificity repertoire of background immunoglobulin-secreting cells of different isotypes. Cell Immunol. 1988;112:371–380. - PubMed
- Bradley L M, Atkins G G, Swain S L. Long-term CD4+ memory T cells from the spleen lack MEL-14, the lymph node homing receptor. J Immunol. 1992;148:324–331. - PubMed
Publication types
MeSH terms
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous