Mycobacterium tuberculosis infection increases the number of osteoclasts and inhibits osteoclast apoptosis by regulating TNF‑α‑mediated osteoclast autophagy

Liu, Wei; Zhou, Juan; Niu, Fangyong; Pu, Feifei; Wang, Zhiwei; Mi, Huang; Zhao, Xiaolong; Yang, Lin; Tao, Pengfei; Xia, Ping; Feng, Jing

doi:10.3892/etm.2020.8903

Cited by 8 publications

(7 citation statements)

References 37 publications

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“…Interestingly this study also reported that infected MC3T3-E1 cells exhibited an increased production of interleukin (IL)-6, a cytokine that increases bone resorption. Liu and co-workers reported an increased number of osteoclasts in human osteoarticular tuberculosis samples and suggest that tumor necrosis factor‑α inhibits the apoptosis of Mycobacterium tuberculosis infected osteoclasts by regulating their autophagy [ 32 ]. Another cytokine that plays a role in Mycobacterium tuberculosis infection is IL-32.…”

Section: Discussionmentioning

confidence: 99%

Microarchitecture of historic bone samples with tuberculosis

Vekszler

Granner

Nebot

et al. 2022

Wien Klin Wochenschr

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SummaryTuberculosis is among the leading causes of death from infectious diseases and affects many organ systems, including the skeleton. Skeletal tuberculosis is an extrapulmonary stage of tuberculosis, which occurs after the early and post-primary pulmonary stages of the disease. The aim of our study was to assess the microarchitecture of historic dry bone samples of subjects who have died of tuberculosis documented by post-mortem examinations. These preparations date to the pre-antibiotic era, and were provided by the Pathological-Anatomical Collection in the “Fools Tower” of the Natural History Museum Vienna (PASiN-NHM).We investigated macerated samples of 20 vertebral bodies, 19 femoral heads, and 20 tibiae of a total of 59 individuals diagnosed with tuberculosis from the nineteenth and early twentieth century. 10 femora and 10 tibiae from body donors that did not exhibit signs of infection and 10 (unaffected) vertebrae kept at the PASiN-NHM were studied as controls. The affected regions of the bone samples (and the corresponding regions of the control bones) were analyzed by microcomputed tomography using a Viscom X 8060 II system. Obtained images were analyzed semi-quantitatively. In samples with tuberculosis, independent of the investigated skeletal region, trabecular defects and decreased trabecular thickness were observed. Cortical porosity was seen in affected vertebrae and tibia; in tuberculous tibiae (but not in the femora) cortical thickness was decreased. In half of the individuals, cortical sclerosis was present; signs of ankylosis were observed mainly at the femoral heads affected with tuberculosis. We conclude that a combination of several alterations at the trabecular compartment could be suggestive of the presence of tuberculosis in historic skeletal remains.

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Section: Discussionmentioning

confidence: 99%

Microarchitecture of historic bone samples with tuberculosis

Vekszler

Granner

Nebot

et al. 2022

Wien Klin Wochenschr

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“…Bone TB primarily occurs through the dissemination of M. tuberculosis bacilli from the respiratory tract to the bones 33 . Enhanced bone resorption and bone loss are characteristic features of bone TB as a result of abnormal activation of osteoclasts 6,7,34 .…”

Section: Discussionmentioning

confidence: 99%

Metabolic switching and cell wall remodelling of Mycobacterium tuberculosis during bone tuberculosis

Kaur

Sharma

Abhishek

et al. 2022

Preprint

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Bone tuberculosis is widely characterized by irreversible bone destruction caused by Mycobacterium tuberculosis . Mycobacterium has the ability to adapt to various environmental stresses by altering its transcriptome in order to establish infection in the host. Thus, it is of critical importance to understand the transcriptional profile of M. tuberculosis during infection in the bone environment compared to axenic cultures of exponentially growing M.tb. In the current study, we characterized the in vivo transcriptome of M. tuberculosis within abscesses or necrotic specimens obtained from patients with bone TB using whole genome microarrays in order to gain insight into the M. tuberculosis adaptive response within this host microenvironment. A total of 914 mycobacterial genes were found to be significantly over-expressed and 1688 were repressed (fold change>2; p-value ≤ 0.05) in human bone TB specimens. Overall, the mycobacteria displayed a hypometabolic state with significant (p ≤ 0.05) downregulation of major pathways involved in translational machinery, cellular and protein metabolism and response to hypoxia. However, significant enrichment (p ≤ 0.05) of amino-sugar metabolic processes, membrane glycolipid biosynthesis, amino acid biosynthesis (serine, glycine, arginine and cysteine) and accumulation of mycolyl-arabinogalactan-peptidoglycan complex suggests possible mycobacterial survival strategies within the bone lesions by strengthening its cell wall and cellular integrity. Data were also screened for M.tb virulence proteins using Virulent-Pred and VICM-Pred tools, which revealed five genes (Rv1046c, Rv1230c, DppD, PE_PGRS26 and PE_PGRS43) with a possible role in the pathogenesis of bone TB. Next, an osteoblast cell line model for bone TB was developed allowing for significant intracellular multiplication of M.tb. Interestingly, three virulence genes (Rv1046c, DppD and PE_PGRS26) identified from human bone TB microarray data were also found to be overexpressed by intracellular M. tuberculosis in osteoblast cell lines. Overall, these data demonstrate that M. tuberculosis alters its transcriptome as an adaptive strategy to survive in the host and establish infection in bone. Additionally, the in vitro osteoblast model we describe may facilitate our understanding of the pathogenesis of bone TB.

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“…TNF was originally shown to induce autophagy in Ewing sarcoma cells ( Djavaheri-Mergny et al., 2006 ). Recently, TNF was demonstrated to promote the autophagy of Mtb -infected osteoclasts and constrain the apoptosis of mature osteoclasts ( Liu W. et al., 2020 ). Furthermore, Liu et al.…”

Section: Autophagy In Tb Patientsmentioning

confidence: 99%

“…Furthermore, Liu et al. suggest that their data describe a novel osteoarticular TB-activated cytokine network where autophagy could have an important role in the pathogenesis of osteoarticular TB, pointing out the use of drugs such as TNF for treating this type of TB ( Liu W. et al., 2020 ). Moreover, IFN-γ augments the autophagy process in macrophages and other cells ( Gutierrez et al., 2004 ; Goletti et al., 2013 ), whereas IL-4, IL-10 and IL-13 inhibited autophagy in murine macrophages and human cell lines ( Harris et al., 2007 ; Park et al., 2011 ).…”

Section: Autophagy In Tb Patientsmentioning

confidence: 99%

Shedding Light on Autophagy During Human Tuberculosis. A Long Way to Go

Pellegrini

Tateosian

Morelli

et al. 2022

Front. Cell. Infect. Microbiol.

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Immunity against Mycobacterium tuberculosis (Mtb) is highly complex, and the outcome of the infection depends on the role of several immune mediators with particular temporal dynamics on the host microenvironment. Autophagy is a central homeostatic mechanism that plays a role on immunity against intracellular pathogens, including Mtb. Enhanced autophagy in macrophages mediates elimination of intracellular Mtb through lytic and antimicrobial properties only found in autolysosomes. Additionally, it has been demonstrated that standard anti-tuberculosis chemotherapy depends on host autophagy to coordinate successful antimicrobial responses to mycobacteria. Notably, autophagy constitutes an anti-inflammatory mechanism that protects against endomembrane damage triggered by several endogenous components or infectious agents and precludes excessive inflammation. It has also been reported that autophagy can be modulated by cytokines and other immunological signals. Most of the studies on autophagy as a defense mechanism against Mycobacterium have been performed using murine models or human cell lines. However, very limited information exists about the autophagic response in cells from tuberculosis patients. Herein, we review studies that face the autophagy process in tuberculosis patients as a component of the immune response of the human host against an intracellular microorganism such as Mtb. Interestingly, these findings might contribute to recognize new targets for the development of novel therapeutic tools to combat Mtb. Actually, either as a potential successful vaccine or a complementary immunotherapy, efforts are needed to further elucidate the role of autophagy during the immune response of the human host, which will allow to achieve protective and therapeutic benefits in human tuberculosis.

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Mycobacterium tuberculosis infection increases the number of osteoclasts and inhibits osteoclast apoptosis by regulating TNF‑α‑mediated osteoclast autophagy

Cited by 8 publications

References 37 publications

Microarchitecture of historic bone samples with tuberculosis

Microarchitecture of historic bone samples with tuberculosis

Metabolic switching and cell wall remodelling of Mycobacterium tuberculosis during bone tuberculosis

Shedding Light on Autophagy During Human Tuberculosis. A Long Way to Go

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