Francisella tularensis Infection of Mice as a Model of Sepsis

Spencer, Charles T.; Muniz, Mireya G Ramos; Setzu, Nicole; Guillen, Michelle A Sanchez

doi:10.1007/978-1-0716-1488-4_8

Cited by 2 publications

(2 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Compared to polymicrobial sepsis, monomicrobial sepsis is more common in humans. There are many protocols available using different bacterial species to induce sepsis (He et al., 2021; LeBlanc & Lefort, 2021; Spencer et al., 2021), while fungal models of sepsis are also prevalent (Carreras et al., 2019; Fajardo et al., 2021). In each of the models, evaluating systemic inflammation, lymphopenia, temperature changes, and weight loss will be guides to determine a sepsis‐causing pathogen dose used.…”

Section: Commentarymentioning

confidence: 99%

Mouse Models of Sepsis

Kannan,

Kim,

Heidarian

et al. 2024

Current Protocols

View full text Add to dashboard Cite

Human sepsis is a complex disease that manifests with a diverse range of phenotypes and inherent variability among individuals, making it hard to develop a comprehensive animal model. Despite this difficulty, numerous models have been developed that capture many key aspects of human sepsis. The robustness of these models is vital for conducting pre‐clinical studies to test and develop potential therapeutics. In this article, we describe four different models of murine sepsis that can be used to address different scientific questions relevant to the pathology and immune response during and after a septic event. Basic Protocol 1 details a non‐synchronous cecal ligation and puncture (CLP) model of sepsis, where mice are subjected to polymicrobial exposure through surgery at different time points within 2 weeks. This variation in sepsis onset establishes each mouse at a different state of inflammation and cytokine levels that mimics the variability observed in humans when they present in the clinic. This model is ideal for studying the long‐term impact of sepsis on the host. Basic Protocol 2 is also a type of polymicrobial sepsis, where injection of a specific amount of cecal slurry from a donor mouse into the peritoneum of recipient mice establishes immediate inflammation and sepsis without any need for surgery. Basic Protocol 3 describes infecting mice with a defined gram‐positive or ‐negative bacterial strain to model a subset of sepsis observed in humans infected with a single pathogen. Basic Protocol 4 describes administering LPS to induce sterile endotoxemia. This form of sepsis is observed in humans exposed to bacterial toxins from the environment. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC.Basic Protocol 1: Non‐synchronous cecal ligation and punctureBasic Protocol 2: Cecal slurry model of murine sepsisBasic Protocol 3: Monomicrobial model of murine sepsisBasic Protocol 4: LPS model of murine sepsis

show abstract

Section: Commentarymentioning

confidence: 99%

Mouse Models of Sepsis

Kannan,

Kim,

Heidarian

et al. 2024

Current Protocols

View full text Add to dashboard Cite

show abstract

“…A dysregulated host response associated with elevated levels of pro-inflammatory cytokines and chemokines is a hallmark of the severity of Francisella infection, progression to sepsis and death ( Mares et al, 2008 ; Sharma et al, 2011 ; Spencer et al, 2021 ). Elevated levels of pro-inflammatory cytokines TNF-α, IL-6 and chemokines are the markers of sepsis.…”

Section: Discussionmentioning

confidence: 99%

Chronically hypertensive transgenic mice expressing human AT1R haplotype-I exhibit increased susceptibility to Francisella tularensis

et al. 2023

View full text Add to dashboard Cite

Age-related illnesses, including hypertension and accompanying metabolic disorders, compromise immunity and exacerbate infection-associated fatalities. Renin-angiotensin system (RAS) is the key mechanism that controls blood pressure. Upregulation of RAS through angiotensin receptor type 1 (AT1R), a G-protein coupled receptor, contributes to the pathophysiological consequences leading to vascular remodeling, hypertension, and end-organ damage. Genetic variations that increase the expression of human AT1R may cause the above pathological outcomes associated with hypertension. Previously we have shown that our chronically hypertensive transgenic (TG) mice containing the haplotype-I variant (Hap-I, hypertensive genotype) of human AT1R (hAT1R) gene are more prone to develop the metabolic syndrome-related disorders as compared to the TG mice containing the haplotype-II variant (Hap-II, normotensive genotype). Since aging and an increased risk of hypertension can impact multiple organ systems in a complex manner, including susceptibility to various infections, the current study investigated the susceptibility and potential effect of acute bacterial infection using a Gram-negative intracellular bacterial pathogen, Francisella tularensis in our hAT1R TG mice. Our results show that compared to Hap-II, F. tularensis-infected aged Hap-I TG mice have significantly higher mortality post-infection, higher bacterial load and lung pathology, elevated inflammatory cytokines and altered gene expression profile favoring hypertension and inflammation. Consistent with worsened phenotype in aged Hap-I mice post-Francisella infection, gene expression profiles from their lungs revealed significantly altered expression of more than 1,400 genes. Furthermore, bioinformatics analysis identified genes associated with RAS and IFN-γ pathways regulating blood pressure and inflammation. These studies demonstrate that haplotype-dependent over-expression of the hAT1R gene leads to enhanced susceptibility and lethality due to F. tularensis LVS infection, which gets aggravated in aged animals. Clinically, these findings will help in exploring the role of AT1R-induced hypertension and enhanced susceptibility to infection-related respiratory diseases.

show abstract

Francisella tularensis Infection of Mice as a Model of Sepsis

Cited by 2 publications

References 27 publications

Mouse Models of Sepsis

Mouse Models of Sepsis

Chronically hypertensive transgenic mice expressing human AT1R haplotype-I exhibit increased susceptibility to Francisella tularensis

Contact Info

Product

Resources

About