Mycoplasmas bovis P48 induces apoptosis in EBL cells via an endoplasmic reticulum stress-dependent signaling pathway

Wu, Xiaochun; Zhang, Shengying; Long, Cuiqin; An, Zhen; Xing, Xiaoyong; Fang, Wen; Bao, Shijun

doi:10.1016/j.vetmic.2021.109013

Cited by 11 publications

(12 citation statements)

References 28 publications

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“…The cell viability was dramatically reduced at a high MOI of 1,000. The findings are in partial agreement with previous work that M. bovis-induced apoptosis in epithelial cells (MAC-T and EBL cells) via a mitochondria-dependent pathway and ER-stress-dependent signaling pathway, respectively (Liu et al, 2020;Wu et al, 2021). Consistent with our previous study, live M. bovis P1 induced around 14-15% apoptosis in BoMac cells (Zhao et al, 2021).…”

Section: Discussionsupporting

confidence: 93%

The attenuated Mycoplasma bovis strain promotes apoptosis of bovine macrophages by upregulation of CHOP expression

Zhang

Lu²,

Jin³

et al. 2022

Front. Microbiol.

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Mycoplasma bovis (M. bovis) is one of the major pathogens in the bovine respiratory disease complex, which includes pneumonia, mastitis, and arthritis and causes a great economic loss in the cattle industry. In China, a live-attenuated vaccine strain M. bovis P150 was obtained by a continuous culture of the wild-type strain M. bovis HB0801 (P1) in vitro for 150 passages. Using the infected bovine macrophage cell line BoMac, this work attempted to investigate the mechanism of P150 attenuation and protective immune response. To begin, we show that M. bovis P150 effectively triggered cytotoxicity and apoptosis in BoMac, although with lower intracellular survival than P1. The transcriptomes of BoMac after infection with M. bovis strains P1 and P150 were sequenced, and bioinformatic analysis identified 233 differentially expressed genes (DEGs), with 185 upregulated and 48 downregulated. Further Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses revealed that the majority of the DEGs were linked to CHOP complex, MAP kinase phosphatase activity and were involved in the IL-17 signaling pathway in immune response, MAPK signaling pathway in signal transduction, and p53 signaling pathway in cell growth and death. Among them, the level of C/EBP homologous protein (CHOP) was significantly upregulated in P150-infected BoMac compared to P1-infected cells at different time points, along with its upstream and downstream genes phosphorylated-PERK, phosphorylated-EIF2α, ATF4, and GADD45A increased in the PERK-dependent ER stress response. The role of CHOP in apoptosis was further verified by M. bovis-induced siCHOP knockdown in BoMac cells. The results showed that CHOP knockdown enhanced P150-induced apoptosis and dramatically increased the M. bovis P1 and P150 intracellular survival, particularly for P150. These data suggest that P150 infection upregulates CHOP expression, which can increase apoptosis and mediate a crosstalk between ER stress and apoptosis during infection, and hence, contribute to high cytotoxicity and low intracellular survival.

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Section: Discussionsupporting

confidence: 93%

The attenuated Mycoplasma bovis strain promotes apoptosis of bovine macrophages by upregulation of CHOP expression

Zhang

Lu²,

Jin³

et al. 2022

Front. Microbiol.

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“…P48, as an important virulence-related membrane protein of M. bovis involved in the adhesion process, its effect on EBL cells has been explored to further explain M. bovis infection mechanism. Remarkably, exogenous P48 protein inhibited EBL cells growth and induced similar apoptosis patterns as M. bovis infection, extracellularly and intracellularly (Wu et al, 2021).…”

Section: Immunity Diagnosis and Therapy Immune Responsementioning

confidence: 73%

Mycoplasmas as Host Pantropic and Specific Pathogens: Clinical Implications, Gene Transfer, Virulence Factors, and Future Perspectives

Dawood

Algharib

Zhao

et al. 2022

Front. Cell. Infect. Microbiol.

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Mycoplasmas as economically important and pantropic pathogens can cause similar clinical diseases in different hosts by eluding host defense and establishing their niches despite their limited metabolic capacities. Besides, enormous undiscovered virulence has a fundamental role in the pathogenesis of pathogenic mycoplasmas. On the other hand, they are host-specific pathogens with some highly pathogenic members that can colonize a vast number of habitats. Reshuffling mycoplasmas genetic information and evolving rapidly is a way to avoid their host’s immune system. However, currently, only a few control measures exist against some mycoplasmosis which are far from satisfaction. This review aimed to provide an updated insight into the state of mycoplasmas as pathogens by summarizing and analyzing the comprehensive progress, current challenge, and future perspectives of mycoplasmas. It covers clinical implications of mycoplasmas in humans and domestic and wild animals, virulence-related factors, the process of gene transfer and its crucial prospects, the current application and future perspectives of nanotechnology for diagnosing and curing mycoplasmosis, Mycoplasma vaccination, and protective immunity. Several questions remain unanswered and are recommended to pay close attention to. The findings would be helpful to develop new strategies for basic and applied research on mycoplasmas and facilitate the control of mycoplasmosis for humans and various species of animals.

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“…M. bovis also elaborates a membrane nuclease known as MnuA, which degrade and overcome the neutrophil extracellular traps; a system employed by neutrophils to trap and kill bacteria ( Mitiku et al., 2018 ). Mycoplasma bovis- induced apoptosis has been reported widely in neutrophils, bovine mammary epithelial cells, and embryonic bovine lung cells ( Jimbo et al., 2017 ; Liu et al., 2020a ; Wu et al., 2021 ;). Transient neutropenia reported by Kauf et al.…”

Section: Bovis Virulence Factorsmentioning

confidence: 99%

Mycoplasma bovis Mastitis

Gelgie

Korsa

Dego

2022

Current Research in Microbial Sciences

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Mycoplasmas bovis P48 induces apoptosis in EBL cells via an endoplasmic reticulum stress-dependent signaling pathway

Cited by 11 publications

References 28 publications

The attenuated Mycoplasma bovis strain promotes apoptosis of bovine macrophages by upregulation of CHOP expression

The attenuated Mycoplasma bovis strain promotes apoptosis of bovine macrophages by upregulation of CHOP expression

Mycoplasmas as Host Pantropic and Specific Pathogens: Clinical Implications, Gene Transfer, Virulence Factors, and Future Perspectives

Mycoplasma bovis Mastitis

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