Gnotobiotic mouse model’s contribution to understanding host–pathogen interactions

Kubelková, Klára; Benuchova, Milota; Kozáková, Hana; Šinkora, Marek; Kročová, Zuzana; Pejchal, Jaroslav; Macela, Aleš

doi:10.1007/s00018-016-2341-8

Cited by 13 publications

(9 citation statements)

References 112 publications

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“…Single colony PCR identified the most abundant aerobic bacteria in the AKR fecal sample as Enterococcus faecalis , Lactobacillus murinus and Escherichia coli . After purification and subculture, we determined that the bacteria in (1:1:1) cocktail experiments orally administered by esophageal gavage to three GF 20-week old SAMP mice (10 6 , 7 CFU/mouse in 400 uL of phosphate buffered saline) reproduced the proportions of the 20-week-old donor AKR/J mice (10:1:1). In split-plot experimentation, then we simultaneously inoculated the same 1:1:1 mixture to 5 different sterile substrates (clean sterile corncob bedding, ground GF irradiated autoclaved diet, and three concentrations of soiled bedding; see experimental designs in Fig.…”

Section: Methodsmentioning

confidence: 99%

‘Cyclical Bias’ in Microbiome Research Revealed by A Portable Germ-Free Housing System Using Nested Isolation

Rodriguez-Palacios

Aladyshkina

Ezeji

et al. 2018

Sci Rep

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Germ-Free (GF) research has required highly technical pressurized HEPA-ventilation anchored systems for decades. Herein, we validated a GF system that can be easily implemented and portable using Nested Isolation (NesTiso). GF-standards can be achieved housing mice in non-HEPA-static cages, which only need to be nested ‘one-cage-inside-another’ resembling ‘Russian dolls’. After 2 years of monitoring ~100,000 GF-mouse-days, NesTiso showed mice can be maintained GF for life (>1.3 years), with low animal daily-contamination-probability risk (1 every 867 days), allowing the expansion of GF research with unprecedented freedom and mobility. At the cage level, with 23,360 GF cage-days, the probability of having a cage contamination in NesTiso cages opened in biosafety hoods was statistically identical to that of opening cages inside (the ‘gold standard’) multi-cage pressurized GF isolators. When validating the benefits of using NesTiso in mouse microbiome research, our experiments unexpectedly revealed that the mouse fecal microbiota composition within the ‘bedding material’ of conventional SPF-cages suffers cyclical selection bias as moist/feces/diet/organic content (‘soiledness’) increases over time (e.g., favoring microbiome abundances of Bacillales, Burkholderiales, Pseudomonadales; and cultivable Enterococcus faecalis over Lactobacillus murinus and Escherichia coli), which in turn cyclically influences the gut microbiome dynamics of caged mice. Culture ‘co-streaking’ assays showed that cohoused mice exhibiting different fecal microbiota/hemolytic profiles in clean bedding (high-within-cage individual diversity) ‘cyclically and transiently appear identical’ (less diverse) as bedding soiledness increases, and recurs. Strategies are proposed to minimize this novel functional form of cyclical bedding-dependent microbiome selection bias.

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Section: Methodsmentioning

confidence: 99%

‘Cyclical Bias’ in Microbiome Research Revealed by A Portable Germ-Free Housing System Using Nested Isolation

Rodriguez-Palacios

Aladyshkina

Ezeji

et al. 2018

Sci Rep

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“…The last step is to address the postulated causal role of the gut microbiome in graft fibrosis. Mouse models can be a useful tool to investigate causality, by observing the phenotypic consequences of microbiome manipulation in gnotobiotic mice (Kubelkova et al 2016). Several experimental mouse models have been developed to study liver fibrosis (Yanguas et al 2016).…”

Section: Objective 3: Moving From Associations To Causality and Clinical Applicationsmentioning

confidence: 99%

The role of the gut microbiome in graft fibrosis after pediatric liver transplantation

Qin

Verkade

2020

Hum Genet

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Liver transplantation (LT) is a life-saving option for children with end-stage liver disease. However, about 50% of patients develop graft fibrosis in 1 year after LT, with normal liver function. Graft fibrosis may progress to cirrhosis, resulting in graft dysfunction and ultimately the need for re-transplantation. Previous studies have identified various risk factors for the post-LT fibrogenesis, however, to date, neither of the factors seems to fully explain the cause of graft fibrosis. Recently, evidence has accumulated on the important role of the gut microbiome in outcomes after solid organ transplantation. As an altered microbiome is present in pediatric patients with end-stage liver diseases, we hypothesize that the persisting alterations in microbial composition or function contribute to the development of graft fibrosis, for example by bacteria translocation due to increased intestinal permeability, imbalanced bile acids metabolism, and/or decreased production of short-chain fatty acids (SCFAs). Subsequently, an immune response can be activated in the graft, together with the stimulation of fibrogenesis. Here we review current knowledge about the potential mechanisms by which alterations in microbial composition or function may lead to graft fibrosis in pediatric LT and we provide prospective views on the efficacy of gut microbiome manipulation as a therapeutic target to alleviate the graft fibrosis and to improve long-term survival after LT.

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“…If this is the case, then not all the cells of the same cell type in the body will respond to infection in an identical way at a given time. From this point of view, the cell, with its functional and secretion profile, rather than the host organism in its entirety, seems to be the primary microbe host (Kubelkova et al, 2016 ). In the case of in vitro Francisella models, the literature presents quite different conclusions concerning the outcome of Francisella innate immune recognition.…”

Section: Conclusion and Prospectsmentioning

confidence: 99%

Innate Immune Recognition: Implications for the Interaction of Francisella tularensis with the Host Immune System

Kročová

Macela

Kubelková

2017

Front. Cell. Infect. Microbiol.

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The intracellular bacterial pathogen Francisella tularensis causes serious infectious disease in humans and animals. Moreover, F. tularensis, a highly infectious pathogen, poses a major concern for the public as a bacterium classified under Category A of bioterrorism agents. Unfortunately, research has so far failed to develop effective vaccines, due in part to the fact that the pathogenesis of intracellular bacteria is not fully understood and in part to gaps in our understanding of innate immune recognition processes leading to the induction of adaptive immune response. Recent evidence supports the concept that immune response to external stimuli in the form of bacteria is guided by the primary interaction of the bacterium with the host cell. Based on data from different Francisella models, we present here the basic paradigms of the emerging innate immune recognition concept. According to this concept, the type of cell and its receptor(s) that initially interact with the target constitute the first signaling window; the signals produced in the course of primary interaction of the target with a reacting cell act in a paracrine manner; and the innate immune recognition process as a whole consists in a series of signaling windows modulating adaptive immune response. Finally, the host, in the strict sense, is the interacting cell.

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Gnotobiotic mouse model’s contribution to understanding host–pathogen interactions

Cited by 13 publications

References 112 publications

‘Cyclical Bias’ in Microbiome Research Revealed by A Portable Germ-Free Housing System Using Nested Isolation

‘Cyclical Bias’ in Microbiome Research Revealed by A Portable Germ-Free Housing System Using Nested Isolation

The role of the gut microbiome in graft fibrosis after pediatric liver transplantation

Innate Immune Recognition: Implications for the Interaction of Francisella tularensis with the Host Immune System

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