Reversible Microbial Colonization of Germ-Free Mice Reveals the Dynamics of IgA Immune Responses

Hapfelmeier, Siegfried; Lawson, Melissa A.; Slack, Emma; Kirundi, Jorum; Stoel, Maaike; Heikenwälder, Mathias; Cahenzli, Julia; Velykoredko, Yuliya; Balmer, Maria L.; Endt, Kathrin; Geuking, Markus B.; Curtiss, Roy; McCoy, Kathy D.; Macpherson, Andrew J.

doi:10.1126/science.1188454

Cited by 708 publications

(675 citation statements)

References 24 publications

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“…[81] When the microbiota is depleted (either in GF or antibiotic-treated animals), the immune response is profoundly altered. [7,81] At least some of these immune irregularities in GF mice can be restored by colonization with a normal microbiota [82] or with specific probiotic strains. [83] Additionally, some probiotics have been shown to attenuate pro-inflammatory profiles in cases of pathogen exposure or clinical disease states.…”

Section: Immune Modulation Is a Key Communication Pathway In The Micrmentioning

confidence: 99%

Gutsy Moves: The Amygdala as a Critical Node in Microbiota to Brain Signaling

et al. 2017

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The amygdala is a key brain area regulating responses to stress and emotional stimuli, so improving our understanding of how it is regulated could offer novel strategies for treating disturbances in emotion regulation. As we review here, a growing body of evidence indicates that the gut microbiota may contribute to a range of amygdala-dependent brain functions from pain sensitivity to social behavior, emotion regulation, and therefore, psychiatric health. In addition, it appears that the microbiota is necessary for normal development of the amygdala at both the structural and functional levels. While further investigations are needed to elucidate the exact mechanisms of microbiota-to-amygdala communication, ultimately, this work raises the intriguing possibility that the gut microbiota may become a viable treatment target in disorders associated with amygdala dysregulation, including visceral pain, post-traumatic stress disorder, and beyond. Also see the video abstract here: https://youtu.be/O5gvxVJjX18

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Section: Immune Modulation Is a Key Communication Pathway In The Micrmentioning

confidence: 99%

Gutsy Moves: The Amygdala as a Critical Node in Microbiota to Brain Signaling

et al. 2017

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“…It was reported recently that the maintenance of intestinal IgA production is significantly different from that of systemic IgG production (8). It was found that, in a germ-free condition, antigenspecific IgA + plasma cells could be maintained in the intestine for a long time in the absence of antigenic stimulation (half-life > 16 wk), suggesting that unique intrinsic properties of the IgAproducing plasma cells and intestinal environments might collaborate to maintain the prolonged IgA production.…”

mentioning

confidence: 93%

Critical roles of chemokine receptor CCR10 in regulating memory IgA responses in intestines

Yang

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Chemokine receptor CCR10 is expressed by all intestinal IgA-producing plasma cells and is suggested to play an important role in positioning these cells in the lamina propria for proper IgA production to maintain intestinal homeostasis and protect against infection. However, interfering with CCR10 or its ligand did not impair intestinal IgA production under homeostatic conditions or during infection, and the in vivo function of CCR10 in the intestinal IgA response remains unknown. We found that an enhanced generation of IgA + cells in isolated lymphoid follicles of intestines offset defective intestinal migration of IgA + cells in CCR10-KO mice, resulting in the apparently normal IgA production under homeostatic conditions and in primary response to pathogen infection. However, the compensatorily generated IgA + cells in CCR10-KO mice carried fewer hypermutations in their Ig heavy chain alleles than those of WT mice, indicating that their IgA repertoires are qualitatively different, which might impact the intestinal homeostasis of microflora. In addition, CCR10-deficient long-lived IgA-producing plasma cells and IgA + memory B cells generated against the pathogen infection could not be maintained properly in intestines. Consequently, IgA memory responses to the pathogen reinfection were severely impaired in CCR10-KO mice. These findings elucidate critical roles of CCR10 in regulating the intestinal IgA response and memory maintenance and could help in design of vaccines against intestinal and possibly other mucosal pathogens.

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“…Such approaches hold tremendous promise for unraveling the contributions of both host and microbiota genetics for coadaptation . Hapfelmeier et al (2010) developed a system of ''reversible colonization'' by developing a triple mutant strain of Escherichia coli K12 with three auxotrophic deletions. When fed to gnotobiotic mice, these live but nonreplicating bacteria resulted in mice that were transiently colonized and, as such, provided a system to probe questions of immunological memory regarding antibacterial IgA production in the gut (Hapfelmeier et al 2010).…”

Section: Engineered Microbiomes In Micementioning

confidence: 99%

“…Hapfelmeier et al (2010) developed a system of ''reversible colonization'' by developing a triple mutant strain of Escherichia coli K12 with three auxotrophic deletions. When fed to gnotobiotic mice, these live but nonreplicating bacteria resulted in mice that were transiently colonized and, as such, provided a system to probe questions of immunological memory regarding antibacterial IgA production in the gut (Hapfelmeier et al 2010). As a result of the facile nature of bacterial genetics, rapidly evolving meta'omics technology, and the surge of interest in gnotobiotics, continued technical ingenuity in highly simplified microbial community mouse model systems should be expected.…”

Section: Engineered Microbiomes In Micementioning

confidence: 99%

Exploring host–microbiota interactions in animal models and humans

2013

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The animal and bacterial kingdoms have coevolved and coadapted in response to environmental selective pressures over hundreds of millions of years. The meta'omics revolution in both sequencing and its analytic pipelines is fostering an explosion of interest in how the gut microbiome impacts physiology and propensity to disease. Gut microbiome studies are inherently interdisciplinary, drawing on approaches and technical skill sets from the biomedical sciences, ecology, and computational biology. Central to unraveling the complex biology of environment, genetics, and microbiome interaction in human health and disease is a deeper understanding of the symbiosis between animals and bacteria. Experimental model systems, including mice, fish, insects, and the Hawaiian bobtail squid, continue to provide critical insight into how host-microbiota homeostasis is constructed and maintained. Here we consider how model systems are influencing current understanding of host-microbiota interactions and explore recent human microbiome studies.The distinctive body plans of animals offer many niches for members of the archaeal and bacterial kingdoms. While the lumen of the human distal gut is one of the most densely populated ecosystems on our planet, humans and other animals harbor several microbiomes on and within their body surfaces such as the respiratory and urogenital tracts and the skin. As the gut has evolved from the relatively simple tube of the ancient cyclostomatida to the more highly compartmentalized gastrointestinal tracts of mammalian species, the diversity and complexity of the microbial inhabitants of those spaces has increased as well (Fig.

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Reversible Microbial Colonization of Germ-Free Mice Reveals the Dynamics of IgA Immune Responses

Cited by 708 publications

References 24 publications

Gutsy Moves: The Amygdala as a Critical Node in Microbiota to Brain Signaling

Gutsy Moves: The Amygdala as a Critical Node in Microbiota to Brain Signaling

Critical roles of chemokine receptor CCR10 in regulating memory IgA responses in intestines

Exploring host–microbiota interactions in animal models and humans

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