@article{7b517efc2f154e728c053e9a05d731b9,
title = "Altered Immunity of Laboratory Mice in the Natural Environment Is Associated with Fungal Colonization",
abstract = "Free-living mammals, such as humans and wild mice, display heightened immune activation compared with artificially maintained laboratory mice. These differences are partially attributed to microbial exposure as laboratory mice infected with pathogens exhibit immune profiles more closely resembling that of free-living animals. Here, we examine how colonization by microorganisms within the natural environment contributes to immune system maturation by releasing inbred laboratory mice into an outdoor enclosure. In addition to enhancing differentiation of T cell populations previously associated with pathogen exposure, outdoor release increased circulating granulocytes. However, these “rewilded” mice were not infected by pathogens previously implicated in immune activation. Rather, immune system changes were associated with altered microbiota composition with notable increases in intestinal fungi. Fungi isolated from rewilded mice were sufficient in increasing circulating granulocytes. These findings establish a model to investigate how the natural environment impacts immune development and show that sustained fungal exposure impacts granulocyte numbers.",
keywords = "Aspergillus, fungi, granulocytes, laboratory mice, mesocosm, microbiota, mycobiota, neutrophils, rewilding, wild mice",
author = "Frank Yeung and Chen, {Ying Han} and Lin, {Jian Da} and Leung, {Jacqueline M.} and Caroline McCauley and Devlin, {Joseph C.} and Christina Hansen and Alex Cronkite and Zac Stephens and Charlotte Drake-Dunn and Yi Fulmer and Bo Shopsin and Ruggles, {Kelly V.} and Round, {June L.} and P'ng Loke and Graham, {Andrea L.} and Ken Cadwell",
note = "Funding Information: K.C. receives research funding from Pfizer and Abbvie and P.L. receives research funding from Pfizer. K.C. has consulted for or received an honorarium from Puretech Health, Genentech, and Abbvie. K.C. has a provisional patent, U.S. Patent Application. No. 15/625,934. P.L. consults for and has equity in Toilabs. P.L. is a federal employee. Funding Information: We wish to thank William Craigens, Daniel Navarrete Prado, Allison Lee, and Veena Chittamuri for assistance with trapping and husbandry in the field and the PU Lab Animal Resources staff for logistical support. We wish to thank the NYU School of Medicine Flow Cytometry and Cell Sorting, Microscopy, Genome Technology, and Histology Cores for use of their instruments and technical assistance (supported in part by National Institutes of Health [NIH] grants P31CA016087 , S10OD01058 , and S10OD018338 ). We also wish to thank Margie Alva, Juan Carrasquillo, and Beatriz Delgado for technical assistance with gnotobiotics. The graphical abstract was created with Biorender.com . This research was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases , National Institutes of Health (NIH), NIH grants DK103788 (K.C. and P.L.), AI121244 (K.C.), HL123340 (K.C.), DK093668 (K.C.), AI130945 (P.L. and K.C.), R01 HL125816 (K.C.), R01 AI140754 (K.C.), HL084312 , AI133977 (P.L.), research station and research rebate awards from PU EEB (A.L.G.), a pilot award from the NYU CTSA (grant UL1TR001445 ) from the National Center for Advancing Translational Sciences (NCATS) (K.C. and P.L.), and pilot awards from the NYU Cancer Center grant P30CA016087 (K.C.), AI100853 (Y.H.C.), and DK122698 (F.Y.). This work was also supported by a Department of Defense grant W81XWH-16-1-0256 (P.L.), Faculty Scholar grant from the Howard Hughes Medical Institute (K.C.), the Crohn{\textquoteright}s & Colitis Foundation (K.C.), the Merieux Institute (K.C.), the Kenneth Rainin Foundation (K.C.), the Stony-Wold Herbert Fund (K.C.), and the Bernard Levine Postdoctoral Research Fellowship in Immunology (Y.H.C.). K.C. is a Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Diseases. Funding Information: We wish to thank William Craigens, Daniel Navarrete Prado, Allison Lee, and Veena Chittamuri for assistance with trapping and husbandry in the field and the PU Lab Animal Resources staff for logistical support. We wish to thank the NYU School of Medicine Flow Cytometry and Cell Sorting, Microscopy, Genome Technology, and Histology Cores for use of their instruments and technical assistance (supported in part by National Institutes of Health [NIH] grants P31CA016087, S10OD01058, and S10OD018338). We also wish to thank Margie Alva, Juan Carrasquillo, and Beatriz Delgado for technical assistance with gnotobiotics. The graphical abstract was created with Biorender.com. This research was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), NIH grants DK103788 (K.C. and P.L.), AI121244 (K.C.), HL123340 (K.C.), DK093668 (K.C.), AI130945 (P.L. and K.C.), R01 HL125816 (K.C.), R01 AI140754 (K.C.), HL084312, AI133977 (P.L.), research station and research rebate awards from PU EEB (A.L.G.), a pilot award from the NYU CTSA (grant UL1TR001445) from the National Center for Advancing Translational Sciences (NCATS) (K.C. and P.L.), and pilot awards from the NYU Cancer Center grant P30CA016087 (K.C.), AI100853 (Y.H.C.), and DK122698 (F.Y.). This work was also supported by a Department of Defense grant W81XWH-16-1-0256 (P.L.), Faculty Scholar grant from the Howard Hughes Medical Institute (K.C.), the Crohn's & Colitis Foundation (K.C.), the Merieux Institute (K.C.), the Kenneth Rainin Foundation (K.C.), the Stony-Wold Herbert Fund (K.C.), and the Bernard Levine Postdoctoral Research Fellowship in Immunology (Y.H.C.). K.C. is a Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Diseases. Design of experiments, data analysis, data discussion, and interpretation: F.Y. Y.-H.C. J.-D.L. J.C.D. P.L. A.L.G. and K.C; primary responsibility for execution of experiments: F.Y. Y.-H.C. J.-D.L. J.M.L. C.M. A.C. Z.S. and C.D.-D.; MLN cell RNA, 16S and ITS sequencing analysis: J.C.D. J.L.R. K.V.R. Z.S. F.Y. and Y.-H.C. Genotyping bacteria isolates: F.Y. Y.F. and B.S. All authors discussed data and commented on the manuscript. K.C. receives research funding from Pfizer and Abbvie and P.L. receives research funding from Pfizer. K.C. has consulted for or received an honorarium from Puretech Health, Genentech, and Abbvie. K.C. has a provisional patent, U.S. Patent Application. No. 15/625,934. P.L. consults for and has equity in Toilabs. P.L. is a federal employee. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = may,
day = "13",
doi = "10.1016/j.chom.2020.02.015",
language = "English (US)",
volume = "27",
pages = "809--822.e6",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "5",
}