PMID- 27403624 OWN - NLM STAT- MEDLINE DCOM- 20171024 LR - 20180605 IS - 1552-4930 (Electronic) IS - 1552-4922 (Linking) VI - 91 IP - 1 DP - 2017 Jan TI - Wild immunology assessed by multidimensional mass cytometry. PG - 85-95 LID - 10.1002/cyto.a.22906 [doi] AB - A great part of our knowledge on mammalian immunology has been established in laboratory settings. The use of inbred mouse strains enabled controlled studies of immune cell and molecule functions in defined settings. These studies were usually performed in specific-pathogen free (SPF) environments providing standardized conditions. In contrast, mammalians including humans living in their natural habitat are continuously facing pathogen encounters throughout their life. The influences of environmental conditions on the signatures of the immune system and on experimental outcomes are yet not well defined. Thus, the transferability of results obtained in current experimental systems to the physiological human situation has always been a matter of debate. Studies elucidating the diversity of "wild immunology" imprintings in detail and comparing it with those of "clean" lab mice are sparse. Here, we applied multidimensional mass cytometry to dissect phenotypic and functional differences between distinct groups of laboratory and pet shop mice as a source for "wild mice". For this purpose, we developed a 31-antibody panel for murine leukocyte subsets identification and a 35-antibody panel assessing various cytokines. Established murine leukocyte populations were easily identified and diverse immune signatures indicative of numerous pathogen encounters were classified particularly in pet shop mice and to a lesser extent in quarantine and non-SPF mice as compared to SPF mice. In addition, unsupervised analysis identified distinct clusters that associated strongly with the degree of pathogenic priming, including increased frequencies of activated NK cells and antigen-experienced B- and T-cell subsets. Our study unravels the complexity of immune signatures altered under physiological pathogen challenges and highlights the importance of carefully adapting laboratory settings for immunological studies in mice, including drug and therapy testing. (c) 2016 International Society for Advancement of Cytometry. CI - (c) 2016 International Society for Advancement of Cytometry. FAU - Japp, Alberto Sada AU - Japp AS AD - Regenerative Immunology and Aging, BCRT, Charite Universitatsmedizin Berlin, Berlin, Germany. FAU - Hoffmann, Kerstin AU - Hoffmann K AD - Regenerative Immunology and Aging, BCRT, Charite Universitatsmedizin Berlin, Berlin, Germany. FAU - Schlickeiser, Stephan AU - Schlickeiser S AD - BCRT Flow Cytometry Lab (BCRT-FCL), BCRT, Charite Universitatsmedizin Berlin, Berlin, Germany. AD - Institute for Medical Immunology, Charite Universitatsmedizin Berlin, Berlin, Germany. FAU - Glauben, Rainer AU - Glauben R AD - Medical Department I (Gastroenterology, Rheumatology, Infectious Diseases), Charite - Universitatsmedizin Berlin, Berlin, Germany. FAU - Nikolaou, Christos AU - Nikolaou C AD - Regenerative Immunology and Aging, BCRT, Charite Universitatsmedizin Berlin, Berlin, Germany. FAU - Maecker, Holden T AU - Maecker HT AD - Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, California. FAU - Braun, Julian AU - Braun J AD - Regenerative Immunology and Aging, BCRT, Charite Universitatsmedizin Berlin, Berlin, Germany. FAU - Matzmohr, Nadine AU - Matzmohr N AD - Regenerative Immunology and Aging, BCRT, Charite Universitatsmedizin Berlin, Berlin, Germany. AD - Federal Office of Consumer Protection and Food Safety (BVL), Berlin, Germany. FAU - Sawitzki, Birgit AU - Sawitzki B AD - Transplantation Tolerance, Institute for Medical Immunology, Charite Universitatsmedizin Berlin, Berlin, Germany. FAU - Siegmund, Britta AU - Siegmund B AD - Medical Department I (Gastroenterology, Rheumatology, Infectious Diseases), Charite - Universitatsmedizin Berlin, Berlin, Germany. FAU - Radbruch, Andreas AU - Radbruch A AD - Deutsches Rheuma-Forschungszentrum, Berlin, Germany. FAU - Volk, Hans-Dieter AU - Volk HD AD - Institute for Medical Immunology, Charite Universitatsmedizin Berlin, Berlin, Germany. FAU - Frentsch, Marco AU - Frentsch M AD - Regenerative Immunology and Aging, BCRT, Charite Universitatsmedizin Berlin, Berlin, Germany. FAU - Kunkel, Desiree AU - Kunkel D AD - BCRT Flow Cytometry Lab (BCRT-FCL), BCRT, Charite Universitatsmedizin Berlin, Berlin, Germany. FAU - Thiel, Andreas AU - Thiel A AD - Regenerative Immunology and Aging, BCRT, Charite Universitatsmedizin Berlin, Berlin, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160712 PL - United States TA - Cytometry A JT - Cytometry. Part A : the journal of the International Society for Analytical Cytology JID - 101235694 SB - IM MH - Animals MH - Humans MH - Image Cytometry/*methods MH - Killer Cells, Natural/*immunology MH - Leukocytes/immunology MH - Mice MH - Mice, Inbred Strains/immunology MH - T-Lymphocyte Subsets/*immunology OTO - NOTNLM OT - Key terms: wild immunology OT - adaptive immune system OT - innate immune system OT - mass cytometry EDAT- 2016/07/13 06:00 MHDA- 2017/10/25 06:00 CRDT- 2016/07/13 06:00 PHST- 2016/03/16 00:00 [received] PHST- 2016/06/06 00:00 [revised] PHST- 2016/06/13 00:00 [accepted] PHST- 2016/07/13 06:00 [pubmed] PHST- 2017/10/25 06:00 [medline] PHST- 2016/07/13 06:00 [entrez] AID - 10.1002/cyto.a.22906 [doi] PST - ppublish SO - Cytometry A. 2017 Jan;91(1):85-95. doi: 10.1002/cyto.a.22906. Epub 2016 Jul 12.