Discordant susceptibility of inbred C57BL/6 versus outbred CD1 mice to experimental fungal sepsis

Carreras, Esther; Andrés, María Velasco de; Orta‐Mascaró, Marc; Simões, Inês; Català, Cristina; Zaragoza, Óscar; Lozano, Francisco

doi:10.1111/cmi.12995

Cited by 11 publications

(14 citation statements)

References 34 publications

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“…While the most widely used strains C57BL/6 and BALB/c express functional TLR4 and are therefore sensitive to LPS, point mutations in the tlr4 gene have rendered some strains (e.g., C3H/HeJ, C57BL10/ScSr) resistant to LPS (191), making them useful tools to study endotoxin-independent host responses (154). However, C57BL/6 are more susceptible to fungal sepsis induced by zymosan or Candida albicans infection than outbred CF-1 mice, showing weaker Th1 response and poor survival (192). Further, mouse strains carrying loss-of-function mutations of complement factor C5 such as DBA/1 or DBA/2 display altered susceptibility to certain bacterial strains.…”

Section: Rodent Models To Study the Role Of Platelets In Sepsismentioning

confidence: 99%

Platelets in Sepsis: An Update on Experimental Models and Clinical Data

et al. 2019

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Beyond their important role in hemostasis, platelets play a crucial role in inflammatory diseases. This becomes apparent during sepsis, where platelet count and activation correlate with disease outcome and survival. Sepsis is caused by a dysregulated host response to infection, leading to organ dysfunction, permanent disabilities, or death. During sepsis, tissue injury results from the concomitant uncontrolled activation of the complement, coagulation, and inflammatory systems as well as platelet dysfunction. The balance between the systemic inflammatory response syndrome (SIRS) and the compensatory anti-inflammatory response (CARS) regulates sepsis outcome. Persistent thrombocytopenia is considered as an independent risk factor of mortality in sepsis, although it is still unclear whether the drop in platelet count is the cause or the consequence of sepsis severity. The role of platelets in sepsis development and progression was addressed in different experimental in vivo models, particularly in mice, that represent various aspects of human sepsis. The immunomodulatory function of platelets depends on the experimental model, time, and type of infection. Understanding the molecular mechanism of platelet regulation in inflammation could bring us one step closer to understand this important aspect of primary hemostasis which drives thrombotic as well as bleeding complications in patients with sterile and infectious inflammation. In this review, we summarize the current understanding of the contribution of platelets to sepsis severity and outcome. We highlight the differences between platelet receptors in mice and humans and discuss the potential and limitations of animal models to study platelet-related functions in sepsis.

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Section: Rodent Models To Study the Role Of Platelets In Sepsismentioning

confidence: 99%

Platelets in Sepsis: An Update on Experimental Models and Clinical Data

et al. 2019

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“…The Candida intravenous challenge is one of the common models to mimic clinical candidemia. However, because of the different characteristics of the mice and strains used, the severity of many models is not consistent (MacCallum and Odds, 2005;Carreras et al, 2019). In order to ensure the consistency of the model, we used the Murine Sepsis Score (MSS) for severity evaluation (Shrum et al, 2014).…”

Section: Murine Sepsis Scorementioning

confidence: 99%

T-Bet Expression Mediated by the mTOR Pathway Influences CD4+ T Cell Count in Mice With Lethal Candida Sepsis

et al. 2020

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The sustained high morbidity and mortality of Candida sepsis are mainly caused by compromise of host immunity. Clinically, it is often manifested as a significant decrease in CD4 + T cell count, although the mechanism is unclear. We established a lethal mice Candida sepsis model and used Murine Sepsis Score to group mice with different disease severity to establish the influence of T-bet expression on CD4 + T cell count in Candida sepsis. We found that CD4 + T cell count decreased in Candida-infected compared to uninfected mice, and the degree of decrease increased with aggravation of sepsis. Expression of T-bet similarly decreased with worsening of sepsis, but it was significantly enhanced in candidiasis in comparison of naïve state. To clarify its possible mechanism, we measured the activity of mammalian target of rapamycin (mTOR), which is a key regulator of T-bet expression. The mTOR pathway was activated after infection and its activity increased with progression of sepsis. We used mice with T-cell-specific knockout of mTOR or tuberous sclerosis complex (TSC)1 to further inhibit or strengthen the mTOR signaling pathway. We found that mTOR deletion mice had a higher CD4 + T cell count by regulating T-bet expression, and the result in TSC1 deletion mice was reversed. These results demonstrate that T-bet expression mediated by the mTOR pathway influences the CD4 + T cell count in mice with Candida sepsis.

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“…Another example of differential susceptibility between inbred and outbred mice to an infectious agent was recently reported by Carreras et al [37].. These investigators found that C57BL/6 mice were more susceptible than CD1 mice to the lethal effects of sepsis induced by intravenous administration of the fungus Candida albicans when compared with C57BL/6 [37]. In another study using a mouse model of Streptococcus suis (S. suis)-induced sepsis and cerebral inflammation, Dominguez-Punaro et al reported that while infection of different inbred strains of mice (e.g.…”

Section: Use Of Outbred Stocks To Study Infectious Diseasesmentioning

confidence: 78%

“…The authors concluded that outbred mice may more accurately reflect the genetic diversity of human immunity to this deadly pathogen. Another example of differential susceptibility between inbred and outbred mice to an infectious agent was recently reported by Carreras et al [37].. These investigators found that C57BL/6 mice were more susceptible than CD1 mice to the lethal effects of sepsis induced by intravenous administration of the fungus Candida albicans when compared with C57BL/6 [37].…”

Section: Use Of Outbred Stocks To Study Infectious Diseasesmentioning

confidence: 90%

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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Discordant susceptibility of inbred C57BL/6 versus outbred CD1 mice to experimental fungal sepsis

Cited by 11 publications

References 34 publications

Platelets in Sepsis: An Update on Experimental Models and Clinical Data

Platelets in Sepsis: An Update on Experimental Models and Clinical Data

T-Bet Expression Mediated by the mTOR Pathway Influences CD4+ T Cell Count in Mice With Lethal Candida Sepsis

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

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