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Adenosine A2A Receptor Activation Alleviated Disease of Mice with Systemic Candida albicans Infection by Regulating
Xia-Nan Wu1, Ke Dong1, Yan Liu1
1Department of Clinical Laboratory, Tangdu Hospital, Airforce Medical University, Xi'an, Shaanxi, People's Republic of China.
Purpose:
The incidence of candidemia, mediated by systemic Candida albicans (C. albicans) infection, was increasing. It is an urgent need to understand the underlying disease mechanisms to identify new therapeutic targets. This study aimed to investigate the roles of adenosine-adenosine receptor signal in systemic C. albicans infection.
Methods:
The candidemia mice models (named CA mice) were established by tail intravenous injection of C. albicans. CA Mice were treated with NECA (a metabolically stable adenosine analogue) or agonists targeting different adenosine receptors (A1R, A2AR, A2BR and A3R). The survival rate, renal fungal load and tissue damage were investigated. Bone marrow-derived macrophages (BMDM) were isolated and cultured to investigate the effects of NECA and adenosine receptor agonist on phagocytosis, killing function and polarization of macrophages.
Results:
In CA mice, we observed that NECA and A2AR agonist treatment significantly alleviated the sepsis score and increased the survival rate. Moreover, the renal injury and fungal load were reduced by NECA and A2AR agonist treatment. However, the other adenosine receptors (ie, A1R, A2BR and A3R) activation have no effect on survival and tissue damage of CA mice. A2AR activation could reduce macrophage infiltration in kidney and the production of inflammatory cytokine IL-6 in CA mice. Moreover, adenosine-A2AR signaling activation could enhance antifungal capacity of macrophages and promoted macrophage polarization toward the M2 subtype.
Conclusion:
Activation of adenosine-A2AR axis promoted macrophage M2 polarization, enhanced host defense against systemic C. albicans infection, and alleviated candidiasis. A2AR activation could be considered as a potential therapeutic strategy in candidemia.
Insights
Activating adenosine A2A receptors (A2AAR) boosts macrophage antifungal activity and M2 polarization, improving survival in systemic Candida albicans infections. This suggests A2AAR activation is a promising therapeutic strategy for candidemia.
Area of Science:
- Immunology
- Infectious Diseases
- Pharmacology
Background:
- Systemic *Candida albicans* infection, or candidemia, is increasing, necessitating research into disease mechanisms and therapeutic targets.
- Understanding the role of adenosine signaling in candidemia is crucial for developing novel treatments.
Purpose of the Study:
- To investigate the role of adenosine-adenosine receptor signaling in systemic *Candida albicans* infection.
- To evaluate the therapeutic potential of targeting adenosine receptors in candidemia.
Main Methods:
- Established a murine model of candidemia by intravenous injection of *C. albicans*.
- Treated mice with NECA (adenosine analogue) or adenosine receptor agonists (A1R, A2AR, A2BR, A3R).
- Assessed survival rates, renal fungal load, tissue damage, and macrophage functions (phagocytosis, killing, polarization).
Main Results:
- NECA and A2AR agonist treatment significantly improved survival rates and reduced renal injury and fungal load in candidemia mice.
- A2AR activation decreased kidney macrophage infiltration and IL-6 production.
- Adenosine-A2AR signaling enhanced macrophage antifungal capacity and promoted M2 polarization.
Conclusions:
- Activation of the adenosine-A2AR axis enhances host defense against systemic *C. albicans* infection.
- A2AR activation promotes M2 macrophage polarization and alleviates candidiasis.
- Targeting the A2AR pathway represents a potential therapeutic strategy for treating candidemia.
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