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Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses.

ABSTRACT: The lower intestine of adult mammals is densely colonized with nonpathogenic (commensal) microbes. Gut bacteria induce protective immune responses, which ensure host-microbial mutualism. The continuous presence of commensal intestinal bacteria has made it difficult to study mucosal immune dynamics. Here, we report a reversible germ-free colonization system in mice that is independent of diet or antibiotic manipulation. A slow (more than 14 days) onset of a long-lived (half-life over 16 weeks), highly specific anticommensal immunoglobulin A (IgA) response in germ-free mice was observed. Ongoing commensal exposure in colonized mice rapidly abrogated this response. Sequential doses lacked a classical prime-boost effect seen in systemic vaccination, but specific IgA induction occurred as a stepwise response to current bacterial exposure, such that the antibody repertoire matched the existing commensal content.

SUBMITTER: Hapfelmeier S

PROVIDER: S-EPMC3923373 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses.

Hapfelmeier Siegfried S Lawson Melissa A E MA Slack Emma E Kirundi Jorum K JK Stoel Maaike M Heikenwalder Mathias M Cahenzli Julia J Velykoredko Yuliya Y Balmer Maria L ML Endt Kathrin K Geuking Markus B MB Curtiss Roy R McCoy Kathy D KD Macpherson Andrew J AJ

Science (New York, N.Y.) 20100601 5986

The lower intestine of adult mammals is densely colonized with nonpathogenic (commensal) microbes. Gut bacteria induce protective immune responses, which ensure host-microbial mutualism. The continuous presence of commensal intestinal bacteria has made it difficult to study mucosal immune dynamics. Here, we report a reversible germ-free colonization system in mice that is independent of diet or antibiotic manipulation. A slow (more than 14 days) onset of a long-lived (half-life over 16 weeks), h ...[more]

PMID: 20576892

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Project description:Colonizing germ-free (GF) zebrafish with specific bacterial species provides the possibility of understanding the influence on host biological processes including gene expression, development, immunity, and behavioral responses. It also enlightens our understanding on the host-microbe interactions within the physiological context of a living host. However, the responses of GF zebrafish to various colonization conditions such as bacterial concentrations, colonization time points, and exposure duration remain unclear. To address this issue, we explored the responses of GF zebrafish by using two bacterial species at varying concentrations, colonization time points and exposure duration. Therefore, we mono-associated GF zebrafish with Escherichia coli DH5α or Bacillus subtilis WB800N at concentrations ranging from 102 to 107 CFU/ml either at 3 day post fertilization (dpf) or 5 dpf for 24 or 48 h. We evaluated the responses of GF zebrafish by analyzing the survival rate, colonization efficiency, nutrients metabolism, intestinal cell proliferation, innate immunity, stress, and behavior responses by comparing it to conventionally raised zebrafish (CONR) and GF zebrafish. The results indicated that the final bacteria concentrations ranging from 102 to 104 CFU/ml did not cause any mortality when GF mono-associated larvae were exposed to either E. coli DH5α or B. subtilis WB800N at 3 or 5 dpf, while concentrations ranging from 106 to 107 CFU/ml increased the mortality, particularly for 5 dpf owing to the decrease in dissolved oxygen level. The E. coli DH5α mainly induced the expression of genes related to nutrients metabolism, cell proliferation and immunity, while B. subtilis WB800N mainly upregulated the expression of genes related to immunity and stress responses. Moreover, our data revealed that GF zebrafish showed higher levels of physical activity than CONR and the microbial colonization reduced the hyperactivity of GF zebrafish, suggesting colonization of bacteria affected behavior characteristics. This study provides useful information on bacterial colonization of GF zebrafish and the interaction between the host and microbiota.

Project description:A two-way relationship between diabetes and periodontitis has been discussed recently. Periodontitis microbiota might affect the immune homeostasis of diabetes, but the molecular mechanism of their interactions is still not clear. The aims of this study were to clarify the possible immune regulatory effects of periodontitis microbiota on diabetes and the correlation between immunomodulation and ectopic colonization. A model of germ-free mice with streptozotocin-induced type 1 diabetes mellitus (T1D), which was orally inoculated with mixed saliva samples for 2 weeks, was used in this study. Those mice were randomly divided into two groups, namely, SP (where the T1D mice were orally inoculated with mixed saliva samples from periodontitis patients) and SH (where the T1D mice were orally inoculated with mixed saliva samples from healthy subjects). Ectopic colonization of saliva microbiota was assessed using culture-dependent method and Sanger sequencing, and the composition of gut microbiota was analyzed using 16S rRNA gene sequencing. Changes in 15 types of immune cells and six cytokines either from the small intestine or spleen were detected by multicolor flow cytometry. The correlation between gut microbiota and immune cells was evaluated by redundancy analysis. Although periodontitis microbiota minorly colonized the lungs, spleens, and blood system, they predominantly colonized the gut, which was mainly invaded by Klebsiella. SH and SP differed in beta diversity of the gut bacterial community. Compared to SH, microbial alteration in small intestine occurred with an increase of Lacticaseibacillus, Bacillus, Agathobacter, Bacteroides, and a decrease of Raoultella in SP. More types of immune cells were disordered in the spleen than in the small intestine by periodontitis microbiota, mainly with a dramatical increase in the proportion of macrophages, plasmacytoid dendritic cells (pDCs), monocytes, group 3 innate lymphoid cells, CD4-CD8- T cells and Th17 cells, as well as a decline of αβT cells in SP. Cytokines of IFNγ, IL17, and IL22 produced by CD4 + T cells as well as IL22 produced by ILCs of small intestine rose in numbers, and the intestinal and splenic pDCs were positively regulated by gut bacterial community in SP. In conclusion, periodontitis microbiota invasion leads to ectopic colonization of the extra-oral sites and immune cells infiltration, which might cause local or systemic inflammation. Those cells are considered to act as a "bridge" between T1D and periodontitis.

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Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses.

Publications

Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses.

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