Attenuation of immune‐mediated bone marrow damage in conventionally housed mice

Li, Jun; Dubois, Wendy; Thovarai, Vishal; Wu, Zhijie; Feng, Xingmin; Peat, Tyler J.; Zhang, Shuling; Sen, Shurjo K.; Trinchieri, Giorgio; Chen, Jichun; Mock, Beverly A.; Young, Neal S.

doi:10.1002/mc.23151

Cited by 5 publications

(5 citation statements)

References 51 publications

(52 reference statements)

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“…Analysis of gut microorganisms revealed significant differences between CVT and SPF mice showing effective transfer of microorganisms from CVB to CVT mice through co-housing. The top three OTUs highly represented in CVB mice and effectively transferred to CVT mice during co-housing were Prevotellaceae, Lactobacillaceae and Rikenellaceae, which is consistent with our previous observation in CByB6F1 mice born and housed in the same conventional facility in which the same three microbial families were most abundant in CVB mice [17].These microbial families offer health benefits, since lack of Prevotellaceae and Rikenellaceae have been associated with Parkinson's disease [21], and liver cirrhosis [22]. In Rag1-/-mice, fecal transplants from wild type donors altered gut bacterial community with increases in Prevotellaceae which were accompanied by increases in total number of BM cells and HSPCs [23].…”

Section: Discussionsupporting

confidence: 90%

“…Recapitulation of adult human immune traits in laboratory mice following co-housing with pet-store mice provided strong evidence showing that restoring physiological microbial exposure in laboratory mice could better model immunological events in humans [ 1 ]. Previously, we found that mice born and raised in a conventional facility (CVB) exert greater ability to suppress foreign T cell activation and to attenuate immune-mediated BM destruction than SPF-housed mice [ 17 ]. As such, we reasoned that a partial enhancement in microbial diversity by exposing laboratory mice to a “conventional” living environment might also augment immune and hematopoietic traits to better serve as models for the study of human diseases.…”

Section: Introductionmentioning

confidence: 99%

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Conventional Co-Housing Modulates Murine Gut Microbiota and Hematopoietic Gene Expression

Chen

Zhang

Feng

et al. 2020

IJMS

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Specific-pathogen-free (SPF) mice have improved hematopoietic characteristics relative to germ-free mice, however, it is not clear whether improvements in hematopoietic traits will continue when the level of microorganism exposure is further increased. We co-housed SPF C57BL/6 mice in a conventional facility (CVT) and found a significant increase in gut microbiota diversity along with increased levels of myeloid cells and T cells, especially effector memory T cells. Through single cell RNA sequencing of sorted KL (c-Kit+Lin−) cells, we imputed a decline in long-term hematopoietic stem cells and an increase in granulocyte-monocyte progenitors in CVT mice with up-regulation of genes associated with cell survival. Bone marrow transplantation through competitive repopulation revealed a significant increase in KSL (c-Kit+Sca-1+Lin−) cell reconstitution in recipients of CVT donor cells which occurred when donors were co-housed for both one and twelve months. However, there was minimal to no gain in mature blood cell engraftment in recipients of CVT donor cells relative to those receiving SPF donor cells. We conclude that co-housing SPF mice with mice born in a conventional facility increased gut microbiota diversity, augmented myeloid cell production and T cell activation, stimulated KSL cell reconstitution, and altered hematopoietic gene expression.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Conventional Co-Housing Modulates Murine Gut Microbiota and Hematopoietic Gene Expression

Chen

Zhang

Feng

et al. 2020

IJMS

Self Cite

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“…As pointed out previously, the large majority of mouse studies use ST and SPF conditions [20]. These data suggest that maintaining bacterial diversity may prove beneficial to patients undergoing HSCT [72].…”

Section: Effect Of Housing Temperature On Survival and Tissue Damagesupporting

confidence: 53%

“…In addition to housing temperature, other environmental factors may significantly influence the onset and severity of other auto-and alloimmune diseases [20]. Li et al reported, using a similar model to the one described in the current study, that BM damage was significantly reduced in mice that were housed at ST under conventional conditions (CC) when compared to mice housed at ST in a standard barrier facility under specific pathogen-free (SPF) conditions [72]. Attenuated disease was associated with greater intestinal bacterial diversity in CC mice vs. that observed in the SPF group.…”

Section: Effect Of Housing Temperature On Survival and Tissue Damagementioning

confidence: 61%

Influence of Housing Temperature and Genetic Diversity on Allogeneic T Cell-Induced Tissue Damage in Mice

Enriquez,

McDaniel Mims,

Stroever

et al. 2023

Pathophysiology

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The objective of this study was to determine how housing temperature and genetic diversity affect the onset and severity of allogeneic T cell-induced tissue damage in mice subjected to reduced intensity conditioning (RIC). We found that adoptive transfer of allogeneic CD4+ T cells from inbred donors into sub-lethally irradiated inbred recipients (I→I) housed at standard housing temperatures (ST; 22–24 °C) induced extensive BM and spleen damage in the absence of injury to any other tissue. Although engraftment of T cells in RIC-treated mice housed at their thermo-neutral temperature (TNT; 30–32 °C) also developed similar BM and spleen damage, their survival was markedly and significantly increased when compared to their ST counterparts. In contrast, the adoptive transfer of allogeneic T cells into RIC-treated outbred CD1 recipients failed to induce disease in any tissue at ST or TNT. The lack of tissue damage was not due to defects in donor T cell trafficking to BM or spleen but was associated with the presence of large numbers of B cells and myeloid cells within these tissues that are known to contain immunosuppressive regulatory B cells and myeloid-derived suppressor cells. These data demonstrate, for the first time, that housing temperature affects the survival of RIC-treated I→I mice and that RIC-conditioned outbred mice are resistant to allogeneic T cell-induced BM and spleen damage.

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“…This is not surprising given the evidence demonstrating that the intestinal microbiota of mice may vary greatly among different animal care facilities and animal vendors [74,75,[78][79][80]. Several laboratories including our own, have shown that the incidence and severity of chronic gut inflammation in different mouse models of inflammatory bowel disease is markedly altered by changing animal care facilities or by purposely altering the gut bacteria [81][82][83][84][85][86][87].…”

Section: Modulation Of Immunity and Inflammation By The Microbiomementioning

confidence: 99%

Genomic, microbial and environmental standardization in animal experimentation limiting immunological discovery

et al. 2020

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Background: The use of inbred mice housed under standardized environmental conditions has been critical in identifying immuno-pathological mechanisms in different infectious and inflammatory diseases as well as revealing new therapeutic targets for clinical trials. Unfortunately, only a small percentage of preclinical intervention studies using well-defined mouse models of disease have progressed to clinically-effective treatments in patients. The reasons for this lack of bench-to-bedside transition are not completely understood; however, emerging data suggest that genetic diversity and housing environment may greatly influence muring immunity and inflammation. Results: Accumulating evidence suggests that certain immune responses and/or disease phenotypes observed in inbred mice may be quite different than those observed in their outbred counterparts. These differences have been thought to contribute to differing immune responses to foreign and/or auto-antigens in mice vs. humans. There is also a growing literature demonstrating that mice housed under specific pathogen free conditions possess an immature immune system that remarkably affects their ability to respond to pathogens and/or inflammation when compared with mice exposed to a more diverse spectrum of microorganisms. Furthermore, recent studies demonstrate that mice develop chronic cold stress when housed at standard animal care facility temperatures (i.e. 22-24°C). These temperatures have been shown alter immune responses to foreign and auto-antigens when compared with mice housed at their thermo-neutral body temperature of 30-32°C. Conclusions: Exposure of genetically diverse mice to a spectrum of environmentally-relevant microorganisms at housing temperatures that approximate their thermo-neutral zone may improve the chances of identifying new and more potent therapeutics to treat infectious and inflammatory diseases.

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Attenuation of immune‐mediated bone marrow damage in conventionally housed mice

Cited by 5 publications

References 51 publications

Conventional Co-Housing Modulates Murine Gut Microbiota and Hematopoietic Gene Expression

Conventional Co-Housing Modulates Murine Gut Microbiota and Hematopoietic Gene Expression

Influence of Housing Temperature and Genetic Diversity on Allogeneic T Cell-Induced Tissue Damage in Mice

Genomic, microbial and environmental standardization in animal experimentation limiting immunological discovery

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