High-dimensional single cell mass cytometry analysis of the murine hematopoietic system reveals signatures induced by ageing and physiological pathogen challenges
Abstract Background Immune ageing is a result of repetitive microbial challenges along with cell intrinsic or systemic changes occurring during ageing. Mice under ‘specific-pathogen-free’ (SPF) conditions are frequently used to assess immune ageing in long-term experiments. However, physiological pa...
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doaj-8d32dcc8dc104467bb34b78befd1178c2021-04-25T11:50:51ZengBMCImmunity & Ageing1742-49332021-04-0118111910.1186/s12979-021-00230-3High-dimensional single cell mass cytometry analysis of the murine hematopoietic system reveals signatures induced by ageing and physiological pathogen challengesChristos Nikolaou0Kerstin Muehle1Stephan Schlickeiser2Alberto Sada Japp3Nadine Matzmohr4Desiree Kunkel5Marco Frentsch6Andreas Thiel7Regenerative Immunology and Aging, BIH Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin BerlinRegenerative Immunology and Aging, BIH Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin BerlinInstitute for Medical Immunology, Charité Universitätsmedizin BerlinRegenerative Immunology and Aging, BIH Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin BerlinRegenerative Immunology and Aging, BIH Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin BerlinFlow & Mass Cytometry Core Facility, Charité – Universitätsmedizin Berlin and Berlin Institute of Health (BIH)Regenerative Immunology and Aging, BIH Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin BerlinRegenerative Immunology and Aging, BIH Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin BerlinAbstract Background Immune ageing is a result of repetitive microbial challenges along with cell intrinsic or systemic changes occurring during ageing. Mice under ‘specific-pathogen-free’ (SPF) conditions are frequently used to assess immune ageing in long-term experiments. However, physiological pathogenic challenges are reduced in SPF mice. The question arises to what extent murine experiments performed under SPF conditions are suited to analyze immune ageing in mice and serve as models for human immune ageing. Our previous comparisons of same aged mice with different microbial exposures, unambiguously identified distinct clusters of immune cells characteristic for numerous previous pathogen encounters in particular in pet shop mice. Results We here performed single cell mass cytometry assessing splenic as secondary and bone marrow as primary lymphoid organ-derived leukocytes isolated from young versus aged SPF mice in order to delineate alterations of the murine hematopoietic system induced during ageing. We then compared immune clusters from young and aged SPF mice to pet shop mice in order to delineate alterations of the murine hematopoietic system induced by physiological pathogenic challenges and those caused by cell intrinsic or systemic changes during ageing. Notably, distinct immune signatures were similarly altered in both pet shop and aged SPF mice in comparison to young SPF mice, including increased frequencies of memory T lymphocytes, effector-cytokine producing T cells, plasma cells and mature NK cells. However, elevated frequencies of CD4+ T cells, total NK cells, granulocytes, pDCs, cDCs and decreased frequencies of naïve B cells were specifically identified only in pet shop mice. In aged SPF mice specifically the frequencies of splenic IgM+ plasma cells, CD8+ T cells and CD4+ CD25+ Treg were increased as compared to pet shop mice and young mice. Conclusions Our study dissects firstly how ageing impacts both innate and adaptive immune cells in primary and secondary lymphoid organs. Secondly, it partly distinguishes murine intrinsic immune ageing alterations from those induced by physiological pathogen challenges highlighting the importance of designing mouse models for their use in preclinical research including vaccines and immunotherapies.https://doi.org/10.1186/s12979-021-00230-3ImmunoagingWild immunologyAdaptive immune systemInnate immune systemBone microenvironmentMass cytometry |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Christos Nikolaou Kerstin Muehle Stephan Schlickeiser Alberto Sada Japp Nadine Matzmohr Desiree Kunkel Marco Frentsch Andreas Thiel |
spellingShingle |
Christos Nikolaou Kerstin Muehle Stephan Schlickeiser Alberto Sada Japp Nadine Matzmohr Desiree Kunkel Marco Frentsch Andreas Thiel High-dimensional single cell mass cytometry analysis of the murine hematopoietic system reveals signatures induced by ageing and physiological pathogen challenges Immunity & Ageing Immunoaging Wild immunology Adaptive immune system Innate immune system Bone microenvironment Mass cytometry |
author_facet |
Christos Nikolaou Kerstin Muehle Stephan Schlickeiser Alberto Sada Japp Nadine Matzmohr Desiree Kunkel Marco Frentsch Andreas Thiel |
author_sort |
Christos Nikolaou |
title |
High-dimensional single cell mass cytometry analysis of the murine hematopoietic system reveals signatures induced by ageing and physiological pathogen challenges |
title_short |
High-dimensional single cell mass cytometry analysis of the murine hematopoietic system reveals signatures induced by ageing and physiological pathogen challenges |
title_full |
High-dimensional single cell mass cytometry analysis of the murine hematopoietic system reveals signatures induced by ageing and physiological pathogen challenges |
title_fullStr |
High-dimensional single cell mass cytometry analysis of the murine hematopoietic system reveals signatures induced by ageing and physiological pathogen challenges |
title_full_unstemmed |
High-dimensional single cell mass cytometry analysis of the murine hematopoietic system reveals signatures induced by ageing and physiological pathogen challenges |
title_sort |
high-dimensional single cell mass cytometry analysis of the murine hematopoietic system reveals signatures induced by ageing and physiological pathogen challenges |
publisher |
BMC |
series |
Immunity & Ageing |
issn |
1742-4933 |
publishDate |
2021-04-01 |
description |
Abstract Background Immune ageing is a result of repetitive microbial challenges along with cell intrinsic or systemic changes occurring during ageing. Mice under ‘specific-pathogen-free’ (SPF) conditions are frequently used to assess immune ageing in long-term experiments. However, physiological pathogenic challenges are reduced in SPF mice. The question arises to what extent murine experiments performed under SPF conditions are suited to analyze immune ageing in mice and serve as models for human immune ageing. Our previous comparisons of same aged mice with different microbial exposures, unambiguously identified distinct clusters of immune cells characteristic for numerous previous pathogen encounters in particular in pet shop mice. Results We here performed single cell mass cytometry assessing splenic as secondary and bone marrow as primary lymphoid organ-derived leukocytes isolated from young versus aged SPF mice in order to delineate alterations of the murine hematopoietic system induced during ageing. We then compared immune clusters from young and aged SPF mice to pet shop mice in order to delineate alterations of the murine hematopoietic system induced by physiological pathogenic challenges and those caused by cell intrinsic or systemic changes during ageing. Notably, distinct immune signatures were similarly altered in both pet shop and aged SPF mice in comparison to young SPF mice, including increased frequencies of memory T lymphocytes, effector-cytokine producing T cells, plasma cells and mature NK cells. However, elevated frequencies of CD4+ T cells, total NK cells, granulocytes, pDCs, cDCs and decreased frequencies of naïve B cells were specifically identified only in pet shop mice. In aged SPF mice specifically the frequencies of splenic IgM+ plasma cells, CD8+ T cells and CD4+ CD25+ Treg were increased as compared to pet shop mice and young mice. Conclusions Our study dissects firstly how ageing impacts both innate and adaptive immune cells in primary and secondary lymphoid organs. Secondly, it partly distinguishes murine intrinsic immune ageing alterations from those induced by physiological pathogen challenges highlighting the importance of designing mouse models for their use in preclinical research including vaccines and immunotherapies. |
topic |
Immunoaging Wild immunology Adaptive immune system Innate immune system Bone microenvironment Mass cytometry |
url |
https://doi.org/10.1186/s12979-021-00230-3 |
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