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The Role of HMGB1 in Invasive Candida albicans Infection

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Abstract

Introduction

High mobility group box 1 (HMGB1) is an important “late” inflammatory mediator in bacterial sepsis. Ethyl pyruvate (EP), an inhibitor of HMGB1, can prevent bacterial sepsis by decreasing HMGB1 levels. However, the role of HMGB1 in fungal sepsis is still unclear. Therefore, we investigated the role of HMGB1 and EP in invasive C. albicans infection.

Methods

We measured serum HMGB1 levels in patients with sepsis with C. albicans infection and without fungal infection, and control subjects. We collected clinical indices to estimate correlations between HMGB1 levels and disease severity. Furthermore, we experimentally stimulated mice with C. albicans and C. albicans + EP. Then, we examined HMGB1 levels from serum and tissue, investigated serum levels of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), determined pathological changes in tissues, and assessed mortality.

Results

Serum HMGB1 levels in patients with severe sepsis with C. albicans infection were elevated. Increased HMGB1 levels were correlated with procalcitonin (PCT), C-reactive protein (CRP), 1,3-β-D-Glucan (BDG) and C. albicans sepsis severity. HMGB1 levels in serum and tissues were significantly increased within 7 days after mice were infected with C. albicans. The administration of EP inhibited HMGB1 levels, decreased tissue damage, increased survival rates and inhibited the release of TNF-α and IL-6.

Conclusions

HMGB1 levels were significantly increased in invasive C. albicans infections. EP prevented C. albicans lethality by decreasing HMGB1 expression and release. HMGB1 may provide an effective diagnostic and therapeutic target for invasive C. albicans infections.

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Acknowledgements

We gratefully acknowledge funding from the National Natural Science Foundation of China (No. 81871608, 81171543) to Hang Sun.

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Author notes

  1. JiaoJiao Wang and ChuanXin Wu have contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China

    JiaoJiao Wang, Jing Cheng & Hang Sun

  2. Department of Hepatobiliary Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China

    ChuanXin Wu & XiaoLong Rao

  3. Department of Laboratory Medicine, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China

    YunYing Wang

  4. Guangzhou Institute of Respiratory Diseases, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

    ChongXiang Chen

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  1. JiaoJiao Wang
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Correspondence to Hang Sun.

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Wang, J., Wu, C., Wang, Y. et al. The Role of HMGB1 in Invasive Candida albicans Infection. Mycopathologia 186, 789–805 (2021). https://doi.org/10.1007/s11046-021-00595-5

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  • DOI: https://doi.org/10.1007/s11046-021-00595-5

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