Microbiome: TLR5 Puts the Brakes On

RESEARCH HIGHLIGHTS

MICROBIOME several gut commensal Firmicutes species could stimulate TLR5. Fluorescence-activated cell sort- motile TLR5 puts the brakes on ing was used to assess the profile of commensal IgA-coated and uncoated bacteria Crossing of the gut mucosal barrier flagellum. Many abundant members in Tlr5−/− mice and wild-type mice. bacteria are by bacteria, which is often flagellum- of the gut microbiota are capable of Although the overall ratios of coated prevented dependent, can lead to chronic producing flagella; however, in the to uncoated bacteria were similar in from crossing inflammation. Reporting in Cell Host intact gut, the levels of flagellin are both, pryosequencing showed that the mucosal & Microbe, Tyler Cullender and col- low. To investigate the factors that there were phylum-level differences leagues now show that, in mice, the control the expression of flagellin in coating in Tlr5−/− mice, with barrier by the pattern recognition receptor Toll-like — and thus bacterial motility — in Firmicutes over-represented and TLR5‑induced receptor 5 (TLR5) has a key role in the gut, Cullender and colleagues Proteobacteria under-represented. production of downregulating production of flagella, used a Tlr5−/− mouse strain. The Finally, the authors showed that anti-flagellin thus preventing this potentially main protective antibody in the antibodies against flagellin inhibit the harmful motility. mucosa is immunoglobulin A (IgA) motility of commensal species and IgA antibodies TLR5 is the innate immune recep- and lower levels of anti-flagellin IgA reduce the expression of flagellin in tor for flagellin, which is the main were found in the cecum and faecal Escherichia coli. Moreover, fluores- protein component of the bacterial pellets of Tlr5−/− mice compared cence in situ hybridization revealed with wild-type mice. By contrast, the that bacterial cells could penetrate levels of biologically active flagellin and breach the mucosal barrier in the in the gut were higher in Tlr5−/− mice large and small intestines in Tlr5−/− than in wild-type mice. The authors mice but not in wild-type mice. then assessed flagella-related gene Together, the data suggest that, expression using a combined shotgun in wild-type mice, motile commensal metatranscriptomics and metagen- bacteria are prevented from crossing omics approach, and found that, the mucosal barrier by the TLR5‑ although the overall composition of induced production of anti-flagellin the gut microbiomes in Tlr5−/− and IgA antibodies, which both immo- wild-type mice were similar, the gene bilize the bacteria and, via an as yet expression patterns differed. The data unknown mechanism, downregulate revealed that genes encoding key flagellar gene expression. elements of the flagellar apparatus Sheilagh Molloy −/− were upregulated in Tlr5 mice and ORIGINAL RESEARCH PAPER Cullender, T. C. et al. mainly belonged to members of the Innate and adaptive immunity interact to quench Firmicutes. The authors also showed microbiome flagellar motility in the gut. Cell Host Microbe 14, 571–581 (2013) that flagella that were harvested from Getty/Photodisc

NATURE REVIEWS | MICROBIOLOGY VOLUME 12 | JANUARY 2014