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The Role of HMGB1 in Invasive Candida albicans Infection

JiaoJiao Wang1, ChuanXin Wu2, YunYing Wang3

  • 1Key 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.

Mycopathologia
|October 5, 2021
PubMed
Abstract

Insights

High mobility group box 1 (HMGB1) is elevated in invasive Candida albicans infections. Ethyl pyruvate (EP) reduces HMGB1, preventing fungal sepsis lethality and offering a potential therapeutic target.

Area of Science:

  • Immunology
  • Infectious Diseases
  • Pharmacology

Background:

  • High mobility group box 1 (HMGB1) is a known inflammatory mediator in bacterial sepsis.
  • The role of HMGB1 in fungal sepsis, specifically invasive Candida albicans infections, remains largely uncharacterized.
  • Ethyl pyruvate (EP) is an established inhibitor of HMGB1, demonstrating efficacy in bacterial sepsis models.

Purpose of the Study:

  • To investigate the role of HMGB1 in invasive Candida albicans infections.
  • To evaluate the therapeutic potential of Ethyl pyruvate (EP) in a model of fungal sepsis.

Main Methods:

  • Serum HMGB1 levels were measured in patients with C. albicans sepsis and controls.
  • Correlations between HMGB1 levels and clinical severity markers (PCT, CRP, BDG) were assessed.
  • Mice were infected with C. albicans and treated with EP, monitoring HMGB1, inflammatory cytokines (TNF-α, IL-6), tissue damage, and mortality.

Main Results:

  • Elevated serum HMGB1 levels were observed in patients with severe C. albicans sepsis, correlating with disease severity markers.
  • HMGB1 levels significantly increased in mice following C. albicans infection.
  • EP administration reduced HMGB1 levels, mitigated tissue damage, decreased pro-inflammatory cytokine release, and improved survival rates.

Conclusions:

  • HMGB1 is significantly upregulated during invasive C. albicans infections.
  • Ethyl pyruvate demonstrates a protective effect against C. albicans-induced lethality by inhibiting HMGB1.
  • HMGB1 presents a promising diagnostic and therapeutic target for invasive fungal infections.
Keywords:
Candida albicansEthyl pyruvateHigh mobility group box 1InflammationSepsis

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