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The Involvement of Immune Cells Between Ischemic Stroke and Gut Microbiota

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Abstract

Ischemic stroke, a disease with high mortality and disability rate worldwide, currently has no effective treatment. The systemic inflammation response to the ischemic stroke, followed by immunosuppression in focal neurologic deficits and other inflammatory damage, reduces the circulating immune cell counts and multiorgan infectious complications such as intestinal and gut dysfunction dysbiosis. Evidence showed that microbiota dysbiosis plays a role in neuroinflammation and peripheral immune response after stroke, changing the lymphocyte populations. Multiple immune cells, including lymphocytes, engage in complex and dynamic immune responses in all stages of stroke and may be a pivotal moderator in the bidirectional immunomodulation between ischemic stroke and gut microbiota. This review discusses the role of lymphocytes and other immune cells, the immunological processes in the bidirectional immunomodulation between gut microbiota and ischemic stroke, and its potential as a therapeutic strategy for ischemic stroke.

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Abbreviations

5-HT:

5-Hydroxytryptamine

ABX:

Antibiotics

ACTH:

Adrenocorticotropic hormone

ANS:

Autonomic nervous system

GBMA:

Gut-brain-microbiota axis

CAN:

Central autonomic network

CNS:

Central nervous system

CRH/CRF:

Corticotropin-releasing hormone/factor

DA:

Dopamine

DAMPs:

Damage-associated molecular patterns

DCs:

Dendritic cells

dMCAO:

Distal middle cerebral artery occlusion

DNTs:

Double-negative T cells

EAE:

Experimental autoimmune encephalomyelitis

ENS:

Enteric nervous system

EVs:

Extracellular vesicles

fMCAO:

Filamentous middle cerebral artery occlusion

FMT:

Fecal microbiota transfer

FOXP3:

Forkhead box P3

GBMA:

Gut-brain-microbiome axis

GF:

Germ-free

HDAC:

Histone deacetylase inhibitors

HMGB1:

High-mobility group box 1 protein

HPA:

Hypothalamic-pituitary-adrenal axis

HSP:

Heat shock protein

IBD:

Inflammatory bowel disease

IFN-γ:

Interferon-γ

IL:

Interleukin

IS:

Ischemic stroke

iNOS:

Inducible nitric oxide synthase

LPS:

Lipopolysaccharide

MCAO:

Middle cerebral artery occlusion

MMP:

Matrix metalloproteinase

MS:

Maternal separation

NE:

Norepinephrine

NPY:

Neuropeptide Y

pMCAO:

Permanent middle cerebral artery occlusion

PP:

Peyer’s patches

ROS:

Reactive oxygen species

SCFAs:

Short-chain fatty acids

SFB:

Segmented filamentous bacteria

SIID:

Stroke-induced immunodepression

SP:

Substance P

SPF:

Specific pathogen-free

TMAO:

Trimethylamine-N-oxide

tMCAO:

Transient middle cerebral artery occlusion

TNF:

Tumor necrosis factor

tPA:

Tissue plasminogen activator

Treg:

Regulatory T cells

VIP:

Vasoactive intestinal peptide

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Acknowledgements

Not applicable.

Funding

This work was supported by the National Natural Science Foundation of China (No. 82171336 and 81870939), Open Project of Sichuan Provincial Key Laboratory for Clinical Immunology Translational Medicine (LCMYZHYX-KFKT202203) and the Fundamental Research Funds for the Central Universities (2042022kf1216) to Xiaoxing Xiong.

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Author notes

  1. Bei Pu and Hua Zhu have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Renmin Hospital of Wuhan University, 99 Zhang Zhidong Rd, Wuhan, Hubei, 430060, People’s Republic of China

    Bei Pu, Hua Zhu, Shenqi Zhang, Zhihong Jian & Xiaoxing Xiong

  2. Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People’s Republic of China

    Bei Pu, Hua Zhu, Lijuan Gu & Xiaoxing Xiong

  3. Organ Transplantation Center, Sichuan Provincial People’s Hospital and School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610000, Sichuan, People’s Republic of China

    Liang Wei

  4. Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 610000, Sichuan, China

    Liang Wei

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  4. Lijuan Gu
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  5. Shenqi Zhang
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  6. Zhihong Jian
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  7. Xiaoxing Xiong
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Contributions

B.P. wrote the initial draft. L.G. contributed to reviewing the literature. Z.H. prepared the figures and table. Z.J. and L.W. collected the literature. X.X. designed the manuscript and prepared the final version. The authors read and approved the final manuscript.

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Correspondence to Zhihong Jian or Xiaoxing Xiong.

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Pu, B., Zhu, H., Wei, L. et al. The Involvement of Immune Cells Between Ischemic Stroke and Gut Microbiota. Transl. Stroke Res. (2023). https://doi.org/10.1007/s12975-023-01151-7

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