Anthocyanin Extract from Purple Sweet Potato Exacerbate Mitophagy to Ameliorate Pyroptosis in Klebsiella pneumoniae Infection

Dong, Guokai; Xu, Nana; Wang, Meng; Zhao, Yunyun; Jiang, Fei; Bu, Huimin; Liu, Jinjuan; Yuan, Bo; Li, Rongpeng

doi:10.3390/ijms222111422

Cited by 18 publications

(8 citation statements)

References 63 publications

(84 reference statements)

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“…Our results revealed that K. pneumoniae infection can lead to cellular pyroptosis depending on the virulence of strains. Excessive pyroptosis caused by hvKp infection promotes cellular and tissue damage in the present study; as reported by Dong et al. (2021) , PSPA treatment can alleviate pulmonary inflammation and injury in K. pneumoniae -infected mice by inhibiting pyroptosis.…”

Section: Discussionsupporting

confidence: 80%

Pyroptosis, apoptosis, and autophagy are involved in infection induced by two clinical Klebsiella pneumoniae isolates with different virulence

Wang

Xin

et al. 2023

Front. Cell. Infect. Microbiol.

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Klebsiella pneumoniae can cause widespread infections and is an important factor of hospital- and community-acquired pneumonia. The emergence of hypervirulent K. pneumoniae poses a serious clinical therapeutic challenge and is associated with a high mortality. The goal of this work was to investigate the influence of K. pneumoniae infection on host cells, particularly pyroptosis, apoptosis, and autophagy in the context of host–pathogen interactions to better understand the pathogenic mechanism of K. pneumoniae. Two clinical K. pneumoniae isolates, one classical K. pneumoniae isolate and one hypervirulent K. pneumoniae isolate, were used to infect RAW264.7 cells to establish an in vitro infection model. We first examined the phagocytosis of macrophages infected with K. pneumoniae. Lactate dehydrogenase (LDH) release test, and calcein-AM/PI double staining was conducted to determine the viability of macrophages. The inflammatory response was evaluated by measuring the pro-inflammatory cytokines and reactive oxygen species (ROS) production. The occurrence of pyroptosis, apoptosis, and autophagy was assessed by detecting the mRNA and protein levels of the corresponding biochemical markers. In addition, mouse pneumonia models were constructed by intratracheal instillation of K. pneumoniae for in vivo validation experiments. As for results, hypervirulent K. pneumoniae was much more resistant to macrophage-mediated phagocytosis but caused more severe cellular damage and lung tissues damage compared with classical K. pneumoniae. Moreover, we found increased expression of NLRP3, ASC, caspase-1, and GSDMD associated with pyroptosis in macrophages and lung tissues, and the levels were much higher following hypervirulent K. pneumoniae challenge. Both strains induced apoptosis in vitro and in vivo; the higher apoptosis proportion was observed in infection caused by hypervirulent K. pneumoniae. Furthermore, classical K. pneumoniae strongly triggered autophagy, while hypervirulent K. pneumoniae weakly activated this process. These findings provide novel insights into the pathogenesis of K. pneumoniae and may form the foundation for the future design of treatments for K. pneumoniae infection.

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Section: Discussionsupporting

confidence: 80%

Pyroptosis, apoptosis, and autophagy are involved in infection induced by two clinical Klebsiella pneumoniae isolates with different virulence

Wang

Xin

et al. 2023

Front. Cell. Infect. Microbiol.

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“…In this study, dietary BA supplementation decreased the expression of the above nine immune-related DEGs and the corresponding signaling pathways. Anthocyanin regulated the innate immune system and reduced bacterial systemic dissemination in mice challenged with Klebsiella pneumoniae (Dong et al, 2021 ) and was used as a nutraceutical strategy to modulate stress and immune response in vertebrates (Khan et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Transcriptome and proteome profile of jejunum in chickens challenged with Salmonella Typhimurium revealed the effects of dietary bilberry anthocyanin on immune function

Zhang,

Wang,

et al. 2023

Front. Microbiol.

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IntroductionThe present study investigated the effects of bilberry anthocyanin (BA) on immune function when alleviating Salmonella Typhimurium (S. Typhimurium) infection in chickens.MethodsA total of 180 newly hatched yellow-feathered male chicks were assigned to three groups (CON, SI, and SI + BA). Birds in CON and SI were fed a basal diet, and those in SI + BA were supplemented with 100 mg/kg BA for 18 days. Birds in SI and SI + BA received 0.5 ml suspension of S. Typhimurium (2 × 109 CFU/ml) by oral gavage at 14 and 16 days of age, and those in CON received equal volumes of sterile PBS.ResultsAt day 18, (1) dietary BA alleviated weight loss of chickens caused by S. Typhimurium infection (P < 0.01). (2) Supplementation with BA reduced the relative weight of the bursa of Fabricius (P < 0.01) and jejunal villus height (P < 0.05) and increased the number of goblet cells (P < 0.01) and the expression of MUC2 (P < 0.05) in jejunal mucosa, compared with birds in SI. (3) Supplementation with BA decreased (P < 0.05) the concentration of immunoglobulins and cytokines in plasma (IgA, IL-1β, IL-8, and IFN-β) and jejunal mucosa (IgG, IgM, sIgA, IL-1β, IL-6, IL-8, TNF-α, IFN-β, and IFN-γ) of S. Typhimurium-infected chickens. (4) BA regulated a variety of biological processes, especially the defense response to bacteria and humoral immune response, and suppressed cytokine–cytokine receptor interaction and intestinal immune network for IgA production pathways by downregulating 6 immune-related proteins.ConclusionIn summary, the impaired growth performance and disruption of jejunal morphology caused by S. Typhimurium were alleviated by dietary BA by affecting the expression of immune-related genes and proteins, and signaling pathways are related to immune response associated with immune cytokine receptors and production in jejunum.

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“…Mouse primary alveolar macrophages (AMs) were isolated as previously described (Dong et al, 2021). In brief, mice were killed, and the thoracic cavity and trachea were exposed.…”

Section: Primary Cells and Cell Linesmentioning

confidence: 99%

Chrysophanol alleviates acute lung injury caused by Klebsiella pneumoniae infection by inhibiting pro‐inflammatory cytokine production

Jiang

et al. 2023

Phytotherapy Research

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Acute lung injury (ALI) caused by acute bacterial infection remains a common life‐threatening lung disease. An increased inflammatory response is the basis for the occurrence and development of ALI. Most antibiotics can only reduce the bacterial load but do not protect from lung damage because of an excessive immune response. Chrysophanol (chrysophanic acid, Chr), as a natural anthraquinone extracted from Rheum palmatum L., has various biological functions, including anti‐inflammatory, anti‐cancer activities, and ameliorative effects on cardiovascular diseases. Considering these properties, we investigated the effect of Chr in Klebsiella pneumoniae (KP)‐induced ALI mice and its potential mechanism. Our results showed that Chr had protective effects against KP‐infected mice, including increased survival rate, decreased bacterial burden, reduced recruitment of immune cells, and reduced reactive oxygen species level of lung macrophages. Chr reduced the expression of inflammatory cytokines by inhibiting the toll‐like receptor 4/nuclear factor kappa‐B (TLR4/NF‐κB) signaling pathway and inflammasome activation and strengthening autophagy. Overactivation of the TLR4/NF‐κB signaling pathway by the activator Neoseptin 3 led to Chr losing control of inflammatory cytokines in cells, resulting in increased cell death. Similarly, overactivation of the c‐Jun N‐terminal kinase signaling pathway using the activator anisomycin resulted in Chr losing its inhibitory effect on NOD‐like receptor thermal protein domain associated protein 3 (NFRP3) inflammasome activation, and cell viability was reduced. In addition, autophagy was blocked by siBeclin1, so Chr could not reduce inflammatory factors, and cell viability was markedly inhibited. Collectively, this work unravels the molecular mechanism underpinning Chr‐alleviated ALI via inhibiting pro‐inflammatory cytokines. Thus, Chr is a potential therapeutic agent for KP‐induced ALI.

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Anthocyanin Extract from Purple Sweet Potato Exacerbate Mitophagy to Ameliorate Pyroptosis in Klebsiella pneumoniae Infection

Cited by 18 publications

References 63 publications

Pyroptosis, apoptosis, and autophagy are involved in infection induced by two clinical Klebsiella pneumoniae isolates with different virulence

Pyroptosis, apoptosis, and autophagy are involved in infection induced by two clinical Klebsiella pneumoniae isolates with different virulence

Transcriptome and proteome profile of jejunum in chickens challenged with Salmonella Typhimurium revealed the effects of dietary bilberry anthocyanin on immune function

Chrysophanol alleviates acute lung injury caused by Klebsiella pneumoniae infection by inhibiting pro‐inflammatory cytokine production

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