Inhibition of macrophage autophagy induced by Salmonella enterica serovar typhi plasmid

Wu, Shuyan; Chu, Yuanyuan; Yang, Yanru; Li, Yuanyuan; He, Peiyan; Zheng, YaJie; Zhang, Chi; Liu, QiuChen; Liu, Han; Huang, Rui

doi:10.2741/4220

Cited by 18 publications

(11 citation statements)

References 27 publications

(34 reference statements)

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“…This might contribute to evasion of immune responses by S. typhi. In addition, our previous data showed that the presence of this plasmid increases the survival of the bacterial pathogen and acts through the mitochondrial pathway to mediate macrophage apoptosis [22]. We thus suggest that pR ST98 enhances the virulence of some clinical S. typhi strains through modulating autophagy and cell death.…”

Section: Discussionmentioning

confidence: 84%

Salmonella enterica Serovar Typhi Plasmid Impairs Dendritic Cell Responses to Infection

et al. 2012

Curr Microbiol

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Salmonella enterica serovar Typhi (S. typhi) evades from innate immunity by expression of a variety of pathogenic factors. The "pR(ST98)" plasmid of S. typhi is involved in multidrug-resistant and virulence of S. typhi. However, its exact effect on host cell function remains elusive. Dendritic cells (DCs) play an important role in shaping immune response against Salmonella. For the purpose of investigation whether pR(ST98) might target DCs involved in adaptive immune response, murine DCs were infected with S. typhi wild type and mutant strains. S. typhi stimulation resulted in up-regulation of costimulatory molecules on DCs. S. typhi wild type resulted in decreased up-regulation of CD40, CD80, and CD86 expression. Experiments with S. typhi pR(ST98) mutant (S. typhi-Δ-pR(ST98)) and S. typhi-Δ-pR(ST98) with a complemented plasmid encoding pR(ST98) (S. typhi-c-pR(ST98)) revealed that pR(ST98) accounts for inhibition of surface molecule expression and functional maturity. S. typhi-Δ-pR(ST98) gave maximal levels of IL-12 and IFN-γ release compared with wild type S. typhi or the complemented strains. In contrast to IL-12 and IFN-γ, IL-10 secretion by S. typhi-Δ-pR(ST98)-infected DCs was significantly lower than induction by S. typhi wild type. This indicates that immunity in response to pR(ST98) is skewed away from a protective Th1 response. Moreover, infection with S. typhi-Δ-pR(ST98) induced autophagy in DCs. We herein demonstrate S. typhi pR(ST98) plays essential roles in modulating DCs maturation, activation, inflammatory responses, and autophagy. Together, these data prove that pR(ST98) targets functions of DCs that are required for T-cell activation. This might contribute to evasion of adaptive immune responses by S. typhi.

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Section: Discussionmentioning

confidence: 84%

Salmonella enterica Serovar Typhi Plasmid Impairs Dendritic Cell Responses to Infection

et al. 2012

Curr Microbiol

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“…Autophagy is an evolutionarily conserved, cellular degradation pathway that eliminates damaged or superfluous proteins and organelles (18,19). Cytosolic material is sequestered in autophagosomes, delivered to lysosomes for degradation, and recycled to sustain cell viability (20).…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-induced autophagy reduces radiosensitivity by the HIF-1α/miR-210/Bcl-2 pathway in colon cancer cells

Sun

Xing

Liu

et al. 2014

International Journal of Oncology

103

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Autophagy is an evolutionarily conserved cellular response to conditions of stress such as hypoxia, which induce radioresistance in cancer cells. We studied the mechanism of action of hypoxia on autophagy and radiosensitivity in colon cancer cells. In the human colon cancer cell lines SW480 and SW620, autophagosomes were analyzed to evaluate autophagy by flow cytometry. The expression of hypoxia inducible factor-1α (HIF-1α), Bcl-2, and miR-210 was detected by western blotting and quantitative real-time polymerase chain reaction (PCR). HIF-1α and miR-210 inhibition was induced by siRNA transfections. Apoptosis detection and colony assays were performed to determine radiosensitivity. HIF-1α and miR-210 showed a significant increase under hypoxic condition. The inhibition of HIF-1α decreased miR-210 expression and autophagy. Silencing of miR-210 upregulated Bcl-2 expression and reduced the survival fraction of colon cancer cells after radiation treatment. Under hypoxia, HIF-1α induces miRNA-210 which in turn enhances autophagy and reduces radiosensitivity by downregulating Bcl-2 expression in colon cancer cells. Our results imply that autophagy contributes to the reduction of radiosensitivity in hypoxic environment, and the process is mediated through the HIF-1α/miR-210/Bcl-2 pathway in human colon cancer cells.

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“…pR (ST98) has a molecular weight of 98.6 × 10 6 Da (about 159 kb), and was first identified and reported by Huang et al (2005). Subsequent studies in their laboratory have shown that mutant Salmonella, harboring a pR (ST98) plasmid deletion, inhibited autophagy in infected macrophages (He et al, 2012;Chu et al, 2014;Wu et al, 2014) and mouse embryonic fibroblasts (Lv et al, 2012), while enhancing Salmonella proliferation within cells and consequently promoting cell death. These results demonstrate that the pR (ST98) plasmid enables Salmonella to escape autophagy.…”

Section: The Escape Mechanism Employed By Salmonella To Evade Host Cementioning

confidence: 99%

Salmonella Interacts With Autophagy to Offense or Defense

Shen

Zhang

et al. 2020

Front. Microbiol.

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Autophagy is an important component of the innate immune system in mammals. Low levels of basic autophagy are sustained in normal cells, to help with the clearance of aging organelles and misfolded proteins, thus maintaining their structural and functional stability. However, when cells are faced with challenges, such as starvation or pathogenic infection, their level of autophagy increases significantly. Salmonella is a facultative intracellular pathogen, which imposes an economic burden on the poultry farming industry and human public health. Previous studies have shown that Salmonella can induce the autophagy of cells following invasion, which to a certain extent helps to protect the cells from bacterial colonization. This review summarizes the latest research in the field of Salmonella-induced autophagy, including: (i) the autophagy induction and escape mechanisms employed by Salmonella during the infection of host cells; (ii) the effect of autophagy on intracellular Salmonella; (iii) the important autophagy adaptors that recognize intracellular Salmonella in host cells; and (iv) the effect of autophagy-modulating drugs on Salmonella infection.

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Inhibition of macrophage autophagy induced by Salmonella enterica serovar typhi plasmid

Cited by 18 publications

References 27 publications

Salmonella enterica Serovar Typhi Plasmid Impairs Dendritic Cell Responses to Infection

Salmonella enterica Serovar Typhi Plasmid Impairs Dendritic Cell Responses to Infection

Hypoxia-induced autophagy reduces radiosensitivity by the HIF-1α/miR-210/Bcl-2 pathway in colon cancer cells

Salmonella Interacts With Autophagy to Offense or Defense

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