Regnase-1 Deficiency Restrains Klebsiella pneumoniae Infection by Regulation of a Type I Interferon Response

Trevejo-Nuñez, Giraldina; Lin, Becky; Fan, Li; Aggor, Felix E.Y.; Biswas, Partha S.; Chen, Kong; Gaffen, Sarah L.

doi:10.1128/mbio.03792-21

Cited by 2 publications

(1 citation statement)

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“…lactis) may act as the predator bacterial to exert their antibacterial property via the generation of bacteriocins (25), and an antibiotic cocktail of ciprofloxacin and metronidazole in drinking water ad libitum to mice for 2 weeks can enhance the relative abundance of Lactococcus lactis (26). Potentially, the antibiotic cocktail containing vancomycin, ampicillin, neomycin, and metronidazole may cause a relative increase in predators bacterial such as Lactococcus (25) and pro-inflammatory bacteria such as Escherichia-Shigella and Klebsiella (27), but decrease the relative abundance of anti-inflammatory bacteria such as Akkermansia (28) and autoimmunity-driven bacteria such as Lactobacillus (29), which further affect the capability of microbiota in controlling intestinal inflammation and immunity (30), with a susceptible micro-environment (31) ready for FMT.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of an Antibiotic Cocktail for Fecal Microbiota Transplantation in Mouse

et al. 2022

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ObjectiveThis study aimed to evaluate the effect of an antibiotic cocktail on gut microbiota and provide a reference for establishing an available mouse model for fecal microbiota transplantation (FMT) of specific microbes.DesignC57BL/6J mice (n = 24) had free access to an antibiotic cocktail containing vancomycin (0.5 g/L), ampicillin (1 g/L), neomycin (1 g/L), and metronidazole (1 g/L) in drinking water for 3 weeks. Fecal microbiota was characterized by 16S rDNA gene sequencing at the beginning, 1st week, and 3rd week, respectively. The mice were then treated with fecal microbiota from normal mice for 1 week to verify the efficiency of FMT.ResultsThe diversity of microbiota including chao1, observed species, phylogenetic diversity (PD) whole tree, and Shannon index were decreased significantly (P < 0.05) after being treated with the antibiotic cocktail for 1 or 3 weeks. The relative abundance of Bacteroidetes, Actinobacteria, and Verrucomicrobia was decreased by 99.94, 92.09, and 100%, respectively, while Firmicutes dominated the microbiota at the phylum level after 3 weeks of treatment. Meanwhile, Lactococcus, a genus belonging to the phylum of Firmicutes dominated the microbiota at the genus level with a relative abundance of 80.63%. Further FMT experiment indicated that the fecal microbiota from the receptor mice had a similar composition to the donor mice after 1 week.ConclusionThe antibiotic cocktail containing vancomycin, ampicillin, neomycin, and metronidazole eliminates microbes belonging to Bacteroidetes, Actinobacteria, and Verrucomicrobia, which can be recovered by FMT in mice.

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Section: Discussionmentioning

confidence: 99%

Evaluation of an Antibiotic Cocktail for Fecal Microbiota Transplantation in Mouse

et al. 2022

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Lung Epithelial Regnase-1 Dampens Local Immune Response but Does Not Worsen Susceptibility to Klebsiella pneumoniae

Lin,

Fan,

Jackson

et al. 2024

ImmunoHorizons

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Klebsiella pneumoniae (KP) presents a global health threat, leading to significant morbidity and mortality due to its multidrug-resistant profile and the limited availability of therapeutic options. To eliminate KP lung infection, the host initiates a robust inflammatory response. One of the host’s mechanisms for mitigating excessive inflammation involves the RNA-binding protein regnase-1 (Reg1, MCPIP1, or ZC3H12A). Reg1 has an RNA binding domain that recognizes stem-loop structures in the 3′ untranslated region of various proinflammatory transcripts, leading to mRNA decay. However, excessive suppression of inflammation by Reg1 results in suboptimal KP control. Reg1 deficiency within the nonhematopoietic compartment confers resistance to KP in the lung. Given that lung epithelium is crucial for KP resistance, we hypothesized that selective deletion of Reg1 in lung epithelial cells might enhance proinflammatory signals, leading to a better control of KP. Our transcriptomic analysis of epithelial cells in KP-infected wild-type mice revealed the presence of three distinct alveolar type 2 cell (AT2) subpopulations (conventional, inflammatory, and cycling) and enrichment of Reg1 in inflammatory AT2 cells. We conditionally deleted Reg1 in lung AT2 cells (ΔReg1), which amplified the local inflammatory response in the lung and increased macrophage cell numbers compared with controls. However, when ΔReg1 mice were subjected to KP infection, there were no significant differences in bacterial burden or survival compared with controls. These findings suggest that the local inflammatory response enhanced by Reg1 deletion in AT2 cells is insufficient to control KP infection.

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Regnase-1 Deficiency Restrains Klebsiella pneumoniae Infection by Regulation of a Type I Interferon Response

Cited by 2 publications

References 50 publications

Evaluation of an Antibiotic Cocktail for Fecal Microbiota Transplantation in Mouse

Evaluation of an Antibiotic Cocktail for Fecal Microbiota Transplantation in Mouse

Lung Epithelial Regnase-1 Dampens Local Immune Response but Does Not Worsen Susceptibility to Klebsiella pneumoniae

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