Endoplasmic Reticulum Stress: Importance in Pathogenesis of Mycobacterium tuberculosis

Sharma, Tarina; Grover, Sonam; Ehtesham, Nasreen Z.; Hasnain, Seyed E.

doi:10.1007/978-981-32-9413-4_14

Tarina Sharma⁴^na1,
Sonam Grover⁵^na1,
Nasreen Z. Ehtesham⁶^na1 &
…
Seyed E. Hasnain^5,7^na1

1075 Accesses

Abstract

Mycobacterium tuberculosis (M.tb), the cause of deadly disease tuberculosis, is an opportunistic pathogen that primarily infects host alveolar macrophages. M.tb has developed several mechanisms to persist in infected host cells and to disseminate the disease. Its pathogenesis mainly depends on its competence to modulate the host machinery for its own benefit. One of the cellular responses triggered by M.tb is endoplasmic reticulum stress in infected macrophages, which eventually disturbs the physiological functioning of the ER. Uncontrolled ER stress activates IRE1, PERK, and ATF6 pathway to induce apoptosis of infected cells. Although apoptosis is known to control and clear the infection in primary stages of infection, in case of M.tb-infected ER stressed macrophages, apoptosis is able to disseminate the pathogen during its advanced stages. M.tb-infected lung granulomas are the preferential site of accumulation of apoptotic macrophages, thereby increasing the risk of disease dissemination. The present chapter will describe the mechanism for ER stress response generated by known M.tb virulence factors such as ESAT-6, HBHA, 38-kDa antigen, and PE_PGRS5. Future insights to describe M.tb infection in respect of eliciting ER stress response-mediated apoptosis and host interacting partners has the potential in identifying novel targets for vaccination and drugs to combat the disease.

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Abbreviations

ATF4:: Activating transcription factor 4
ATF6:: Activating transcription factor 6
bZiP:: Basic leucine zipper
CHOP:: C/EBP homologous protein
CREB:: cAMP response element binding
ER:: Endoplasmic reticulum
ERAD:: ER-associated degradation
ERSE:: ERS response elements
GRP78:: 78-kDA glucose regulated protein
HBHA :: Heparin-binding hemagglutinin antigen
Hsp70:: Heat shock protein family
IP3R:: Inositol 1,4,5-triphate receptor
IRE1:: Inositol requiring enzyme 1a
JNK:: Jun-N-terminal kinase
M.tb :: Mycobacterium tuberculosis
MAPK:: Mitogen-activated protein kinases
MCPIP:: MCP-1- induced protein
MPTP:: Mitochondrial permeability transition pore
NO:: Nitric oxide
PERK:: Protein kinase-like ER kinase
ROS:: Reactive oxygen species
SERCA:: Sarco-endoplasmic reticulum calcium ATPase
TB:: Tuberculosis
TLR:: Toll-like receptor
TRAF2:: TNF-receptor associated factor 2
UPR :: Unfolded protein response
UPRE:: UPR element
XBP1:: X-box binding protein 1

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Tarina Sharma and Sonam Grover have equally contributed to this chapter.

Authors and Affiliations

Molecular Infection and Functional Biology Lab, Kusuma School of Biological Sciences, Indian Institute of Technology-Delhi, New Delhi, Delhi, India
Tarina Sharma
JH Institute of Molecular Medicine, Jamia Hamdard, New Delhi, Delhi, India
Sonam Grover & Seyed E. Hasnain
Inflammation Biology and Cell Signaling Laboratory, ICMR-National Institute of Pathology, Safdarjung Hospital Campus, New Delhi, Delhi, India
Nasreen Z. Ehtesham
Dr Reddy’s Institute of Life Sciences, University of Hyderabad Campus, Hyderabad, India
Seyed E. Hasnain

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Tarina Sharma
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Sonam Grover
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Nasreen Z. Ehtesham
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Seyed E. Hasnain
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Editors and Affiliations

JH Institute of Molecular Medicine, Jamia Hamdard, New Delhi, Delhi, India
Seyed Ehtesham Hasnain
Inflammation Biology and Cell Signaling Laboratory, ICMR-National Institute of Pathology, Safdarjung Hospital Campus, New Delhi, Delhi, India
Nasreen Z. Ehtesham
JH Institute of Molecular Medicine, Jamia Hamdard, New Delhi, Delhi, India
Sonam Grover

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Sharma, T., Grover, S., Ehtesham, N.Z., Hasnain, S.E. (2019). Endoplasmic Reticulum Stress: Importance in Pathogenesis of Mycobacterium tuberculosis. In: Hasnain, S., Ehtesham, N., Grover, S. (eds) Mycobacterium Tuberculosis: Molecular Infection Biology, Pathogenesis, Diagnostics and New Interventions. Springer, Singapore. https://doi.org/10.1007/978-981-32-9413-4_14

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DOI: https://doi.org/10.1007/978-981-32-9413-4_14
Published: 01 December 2019
Publisher Name: Springer, Singapore
Print ISBN: 978-981-32-9412-7
Online ISBN: 978-981-32-9413-4
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