Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Uttar Pradesh 226014, India.
Correspondence Address: Prof. Jayantee Kalita, Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebarli Road Lucknow, Uttar Pradesh 226014, India. E-mail:
© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
The survival of any eukaryotic cell may have a unified theory i.e., energy production and clearance of unwanted organelles or pathogens which may be biological or non-biological. Survival of species over time depends not only on survival of cell but also on its ability to replicate and produce progeny. For these functions, intricate genetic, immunological responses including innate and adaptive immunity and congenial environment are needed. Autophagy is one of such mechanism and considered as a housekeeping system of a eukaryotic cell. Takeshige et al. in 1990’s first time elucidated the underlying mechanism for “autophagy” in yeast and showed that same type of fundamental mechanism is used by cells for degrading and recycling cellular components for which the group leader Yoshinori Ohsumi has been awarded Nobel prize in 2016. In last three decades, the role of autophagy has been extensively studied to understand the pathophysiology and to derive possible treatment options in both acute and chronic neurological diseases such as stroke, trauma, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis etc.[2-4]. Recently, the role of autophagy has been evaluated in neuroinfectious diseases especially to understand reactivation of latent virus, persistence and replication of RNA virus, immune enhancement leading to severe disease manifestations and survival of pathogenic organism against a hostile antibiotic treatment evading its action leading to drug resistance. This review article by Sahu and Ter has reviewed the role of autophagy in central nervous system (CNS) infection.
Amongst the different types of autophagy, macroautophagy is the most extensively studied and well characterized[9,10]. The role of micro-autophagy, chaperon mediated autophagy and xenophagy in central nervous system infections yet to be evaluated for bed side application. The immune regulation in CNS is quite different from systemic immune regulation. CNS mostly depends on microglial mediated immune regulation in presence of normal blood brain barrier and blood-cerebrospinal fluid barrier. However, CNS may suffer from double crash immune dysregulation in presence of CNS infection due to haematogenous dissemination of virus, bacteria, parasite or fungus, or meningitis in which natural barriers are lost. Autophagy activation in this situation may be due to adaptive immune signalling through pattern recognition or by secretive pro-inflammatory cytokines (for example tumor necrosis factor-α and interferon-γ) following infections. Autophagy can go in both ways, its activation may clear the micro-organism or the micro-organism may use autophagic activation for their benefit and survival. This immune mediated autophagic process is highly regulated by a number of up and down regulating genes. This may be the reason why some organisms provide different disease severity in different individuals or even in the same individual in the subsequent infection. There are many unresolved questions - Does the different organ system have customized autophagy operating system or have uniform operating system? How much autophagy activation is needed for clearance of pathogens and development of protective adaptive immunity? Is it possible to explore the survival autophagy response in adverse situation, the way saprophytic bacteria lives days to years? The resolution of these questions may pave the way for potential new treatment.
We thanks Mr. Shakti Kumar for secretarial help.Authors’ contributions
Concept, literature search, manuscript preparation and review: Kalita J
Concept, manuscript review: Misra UK
Literature search, manuscript review: Kumar AFinancial support and sponsorship
None.Conflicts of interest
There are no conflicts of interest.Patient consent
Not applicable.Ethics approval
© The Author(s) 2018.
1. Takeshige K, Baba M, Tsuboi S, Noda T, Ohsumi Y. Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction. J Cell Biol 1992;119:301-11.DOIPubMed
2. He SY, Wang CD, Dong HY, Xia FC, Zhou H, Jiang XS, Pei CY, Ren H, Li HS, Li R, Xu HW. Immune-related GTPase M (IRGM1) regulates neuronal autophagy in a mouse model of stroke. Autophagy 2012;8:1621-7.DOIPubMedPMC
3. Alam J, Scheper W. Targeting neuronal MAPK14/p38α activity to modulate autophagy in the Alzheimer disease brain. Autophagy 2016;12:2516-20.DOIPubMedPMC
4. Ahmed I, Liang YD, Schools S, Dawson VL, Dawson TM, Savitt JM. Development and characterization of a new Parkinson disease model resulting from impaired autophagy. J Neurosci 2012;32:16503-9.DOIPubMedPMC
5. Pratt ZL, Sugden B. How human tumor viruses make use of autophagy. Cells 2012;1:617-30.DOIPubMedPMC
6. Katzenell S, Leib DA. Herpes simplex virus and interferon signaling induce novel autophagic clusters in sensory neurons. J Virol 2016;90:4706-19.DOIPubMedPMC
7. Yuk JM, Yoshimori T, Jo EK. Autophagy and bacterial infectious diseases. Exp Mol Med 2012;44:99-108.DOIPubMedPMC
8. Sahu PS, Ter E. Interactions between neurotropic pathogens, neuroinflammatory pathways, and autophagic neural cell death. Neuroimmunol Neuroinflammation 2018;5:2.DOI
9. Zheng L, Terman A, Hallbeck M, Dehvari N, Cowburn RF, Benedikz E, Kågedal K, Cedazo-Minguez A, Marcusson J. Macroautophagy-generated increase of lysosomal amyloid β-protein mediates oxidant-induced apoptosis of cultured neuroblastoma cells. Autophagy 2011;7:1528-45.DOIPubMedPMC
10. Pajares M, Jiménez-Moreno N, García-Yagüe AJ, Escoll M, de Ceballos ML, Van Leuven F, Rábano A, Yamamoto M, Rojo AI, Cuadrado A. Transcription factor NFE2L2/NRF2 is a regulator of macroautophagy genes. Autophagy 2016;12:1902-16.DOIPubMedPMC
11. Iovino F, Orihuela CJ, Moorlag HE, Molema G, Bijlsma JJE. Interactions between blood-borne streptococcus pneumoniae and the blood-brain barrierpreceding meningitis. PLoS One 2013;8:e68408.DOIPubMedPMC
12. Deretic V. Multiple regulatory and effector roles of autophagy in immunity. Curr Opin Immunol 2009;21:53-62.DOIPubMedPMC
13. Choi Y, Bowman JW, Jung JU. Autophagy during viral infection-a double-edged sword. Nat Rev Microbiol 2018; doi: 10.1038/s41579-018-0003-6.DOI