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Updated: Jun 25, 2026

Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
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Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis

Published on: March 19, 2019

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Akt-2 Is a Potential Therapeutic Target for Disseminated Candidiasis

Ling Huang1,2,3, Yilei Ma1, Hui Guo1

  • 1Department of Pathology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA.

Journal of Immunology (Baltimore, Md. : 1950)
|September 21, 2022
PubMed

Insights

Mice lacking Akt-2, but not Akt-1, show enhanced protection against Candida albicans infection. Akt-2 inhibition boosts immune cell activity, suggesting it as a target for treating fungal sepsis.

Area of Science:

  • Immunology
  • Molecular Biology
  • Microbiology

Background:

  • The serine/threonine Akt family, including Akt-1 and Akt-2 isoforms, is crucial for immune response regulation.
  • The specific roles of Akt-1 and Akt-2 in antifungal innate immunity remain largely unexplored.

Purpose of the Study:

  • To investigate the involvement of Akt-1 and Akt-2 in innate immune responses against Candida albicans infection.
  • To determine if Akt-2 inhibition could serve as a therapeutic strategy for fungal sepsis.

Main Methods:

  • Utilizing Akt2 knockout (Akt2-/-) and Akt1 knockout (Akt1-/-) mouse models.
  • Administering specific Akt-2 and Akt-1 inhibitors to C57BL/6 mice.
  • Assessing immune cell recruitment (neutrophils, macrophages) to the spleen.
  • Measuring reactive oxygen species (ROS) production, oxidative burst, myeloperoxidase activity, and NETosis.

Main Results:

  • Akt2-/- mice, unlike Akt1-/- mice, exhibited significant protection against lethal Candida albicans infection.
  • Loss of Akt-2 led to increased neutrophil and macrophage recruitment to the spleen.
  • Akt-2 deficiency enhanced reactive oxygen species expression, oxidative burst, myeloperoxidase activity, and NETosis in immune cells.
  • Pharmacological inhibition of Akt-2, but not Akt-1, conferred protection against lethal fungal infection.

Conclusions:

  • Akt-2 plays an inhibitory role in antifungal innate immunity.
  • Akt-2 suppresses key immune mechanisms including neutrophil and macrophage recruitment and oxidative burst.
  • Targeting Akt-2 presents a promising therapeutic avenue for combating fungal sepsis.

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