Microbiota-innate immune interactions

How do the microbiota impact host metabolism? One way is by causing a low-grade metabolic inflammation. Dysregulation of the interplay between gut microbes and the innate immune system is one way that metabolic inflammation can develop (Vijay-Kumar, 2010). We have a long-running collaboration with Andrew Gewirtz (Georgia State University) and colleagues to look into how toll-like receptor 5 (TLR5), the innate immune receptor that recognizes flagellin (a component of the bacterial flagellum) interacts with the gut microbiome (Tran, 2019). We have shown that TLR5-deficiency results in an overall increase in the expression of motility genes in the gut microbiome, likely mediated through altered antibody responses (Cullender, 2013). Current work focuses on how flagellins of commensal bacteria differ from those of pathogens in their interactions with TLR5.

  • Vijay-Kumar M, Aitken JD, Carvalho FA, Mwangi S, Srinivasa S, Sitaraman SV, Cullender T, Knight R, Ley RE and Gewirtz AT. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science 328: 228-231 (2010)
  • Carvalho FA, Koren O, Johansson M, Nalbantoglu I, Aitken JD, Su Y, Walters WA, González Peña A, Clemente JC, Barnich N, Darfeuille-Michaud A, Vijay-Kumar M, Knight R, Ley RE and Gewirtz AT. Transient inability to manage Proteobacteria promotes chronic gut inflammation in TLR5-deficient mice. Cell Host & Microbe 12: 139-152 (2012)
  • Cullender TC, Chassaing B, Janzon A, Kumar K, Muller C, Werner JJ, Angenent LT, Bell ME, Hay AG, Peterson DA, Walter J, Vijay-Kumar M, Gewirtz AT and Ley RE. Innate and adaptive immunity interact to quench microbiome flagellar motility in the gut. Cell Host & Microbe 14: 571-581 (2013)
  • Chassaign B, Ley RE and Gewirtz AT. Intestinal epithelial cell Toll-like Receptor 5 regulates the intestinal microbiota to prevent low-grade inflammation and metabolic syndrome in mice. Gastroenterology S0016-5085(14)01072-5 (2014)
  • Tran HQ, Ley RE, Gewirtz AT and Chassaing B. Flagellin-elicited adaptive immunity suppresses flagellated microbiota and vaccinates against chronic inflammatory diseases. Nature Communications 10: 5650 (2019)