@article{817abcab3e814f43ae9f365a29c32080,
title = "Microbial antigen encounter during a preweaning interval is critical for tolerance to gut bacteria",
abstract = "We have a mutually beneficial relationship with the trillions of microorganisms inhabiting our gastrointestinal tract. However, maintaining this relationship requires recognizing these organisms as affable and restraining inflammatory responses to these organisms when encountered in hostile settings. How and when the immune system develops tolerance to our gut microbial members is not well understood. We identify a specific preweaning interval in which gut microbial antigens are encountered by the immune system to induce antigen-specific tolerance to gut bacteria. For some bacterial taxa, physiologic encounters with the immune system are restricted to this interval, despite abundance of these taxa in the gut lumen at later times outside this interval. Antigen-specific tolerance to gut bacteria induced during this preweaning interval is stable and maintained even if these taxa are encountered later in life in an inflammatory setting. However, inhibiting microbial antigen encounter during this interval or extending these encounters beyond the normal interval results in a failure to induce tolerance and robust antigen-specific effector responses to gut bacteria upon reencounter in an inflammatory setting. Thus, we have identified a defined preweaning interval critical for developing tolerance to gut bacteria and maintaining the mutually beneficial relationship with our gut microbiota.",
author = "Knoop, {Kathryn A.} and Gustafsson, {Jenny K.} and McDonald, {Keely G.} and Kulkarni, {Devesha H.} and Coughlin, {Paige E.} and Stephanie McCrate and Dongyeon Kim and Hsieh, {Chyi Song} and Hogan, {Simon P.} and Elson, {Charles O.} and Tarr, {Phillip I.} and Newberry, {Rodney D.}",
note = "Funding Information: We thank M. J. Miller for insightful critiques and assistance with 2P imaging and analysis. The 2P imaging was performed at the In Vivo Imaging Core at Washington University School of Medicine. The Washington University Digestive Diseases Research Center Core (DDRCC) Gnotobiotic Facility, supported by NIH grant P30 DK052574, provided the germ-free mice. The High Speed Cell Sorter Core at the Alvin J. Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis, MO, supported in part by National Cancer Institute Cancer Center Support Grant P30 CA91842, provided flow cytometric cell sorting services. The Speed Congenics Facility of the Rheumatic Diseases Core Center, supported by NIH grant P30AR048335, bred the Myd88−/− mice onto the C57BL/6 background. R.D.N., K.G.M., and K.A.K. are inventors on a provisional patent application 62/450,831 held/submitted by Washington University School of Medicine in St. Louis that covers approaches to control dietary and microbial exposure in early life. P.I.T. has equity in, is a member of the scientific advisory board, and is a consultant to MediBeacon Inc., a company that is developing technology to measure gut permeability in humans and is also a co-inventor of a patent that could generate royalty payments. This study was supported by the following grants: AI131342 (R.D.N. and P.I.T.), DK097317 (R.D.N.), AI1126260 (S.P.H. and R.D.N.), Children{\textquoteright}s Discovery Institute grant MD-II-2015-481 (R.D.N. and P.I.T.), P30 DK052574, and DK109006 (K.A.K.). D.H.K. is supported by a Research Fellowship Award from the Crohn{\textquoteright}s and Colitis Foundation of America. Publisher Copyright: Copyright {\textcopyright} 2017 The Authors.",
year = "2017",
doi = "10.1126/sciimmunol.aao1314",
language = "English",
volume = "2",
journal = "Science Immunology",
issn = "2470-9468",
number = "18",
}