Related Experiment Video
Updated: Apr 20, 2026
A Soluble Tetrazolium-Based Reduction Assay to Evaluate the Effect of Antibodies on Candida tropicalis Biofilms
Published on: September 16, 2022
Protection from systemic Candida albicans infection by inactivation of the Sts phosphatases
Shamoon Naseem1, David Frank2, James B Konopka1
1Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA.
Abstract:
The human fungal pathogen Candida albicans causes invasive candidiasis, characterized by fatal organ failure due to disseminated fungal growth and inflammatory damage. The suppressor of TCR signaling 1 (Sts-1) and Sts-2 are two homologous phosphatases that negatively regulate signaling pathways in a number of hematopoietic cell lineages, including T lymphocytes, mast cells, and platelets. Functional inactivation of both Sts enzymes leads to profound resistance to systemic infection by C. albicans, such that greater than 80% of mice lacking Sts-1 and -2 survive a dose of C. albicans (2.5 × 10(5) CFU/mouse) that is uniformly lethal to wild-type mice within 10 days. Restriction of fungal growth within the kidney occurs by 24 h postinfection in the mutant mice. This occurs without induction of a hyperinflammatory response, as evidenced by the decreased presence of leukocytes and inflammatory cytokines that normally accompany the antifungal immune response. Instead, the absence of the Sts phosphatases leads to the rapid induction of a unique immunological environment within the kidney, as indicated by the early induction of a proinflammatory cytokine (CXL10). Mice lacking either Sts enzyme individually display an intermediate lethality phenotype. These observations identify an opportunity to optimize host immune responses toward a deadly fungal pathogen.
Insights
Mice lacking Sts-1 and Sts-2 phosphatases show resistance to deadly Candida albicans infections. This resistance involves restricted fungal growth and a unique immune response in the kidney, offering new strategies against invasive candidiasis.
Area of Science:
- Immunology
- Mycology
- Molecular Biology
Background:
- Invasive candidiasis, caused by Candida albicans, leads to organ failure and death.
- Suppressor of TCR signaling (Sts)-1 and Sts-2 are phosphatases that negatively regulate immune cell signaling.
- Understanding immune evasion mechanisms is crucial for treating fungal infections.
Purpose of the Study:
- To investigate the role of Sts-1 and Sts-2 in host defense against Candida albicans.
- To determine the immunological mechanisms underlying resistance to invasive candidiasis.
- To explore therapeutic strategies targeting Sts phosphatases.
Main Methods:
- Generation and infection of mice lacking Sts-1 and/or Sts-2 with Candida albicans.
- Assessment of survival rates, fungal burden in kidneys, and immune cell/cytokine profiles.
- Analysis of gene expression and signaling pathways in immune cells.
Main Results:
- Mice lacking both Sts-1 and Sts-2 exhibited >80% survival against a lethal C. albicans dose, unlike wild-type mice.
- Fungal growth was restricted in the kidneys of mutant mice within 24 hours post-infection.
- Absence of Sts phosphatases induced a unique proinflammatory cytokine (CXCL10) response without hyperinflammation.
Conclusions:
- Dual inactivation of Sts-1 and Sts-2 confers significant resistance to invasive candidiasis.
- Sts phosphatases regulate key immune responses critical for controlling C. albicans.
- Targeting Sts phosphatases presents a potential strategy for enhancing host immunity against fungal pathogens.
