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PANoptosis opens new treatment options for allergic bronchopulmonary aspergillosis
Dalan Smallwood1, Richard F Lockey1, Narasaiah Kolliputi1
1Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa Fla.
Background:
Allergic bronchopulmonary aspergillosis (ABPA) is a rare airway disorder primarily affecting patients with asthma and cystic fibrosis. Persistent airway inflammation brought on by Aspergillus fumigatus exacerbates the underlying condition and can cause significant respiratory damage. Treatments center on reducing inflammation with the use of corticosteroids and antifungals. PANoptosis is a new concept in the field of cell death and inflammation that posits the existence of cross talk and a master control system for the 3 programmed cell death (PCD) pathways, namely, apoptosis, pyroptosis, and necroptosis. This concept has revolutionized the understanding of PCD and opened new avenues for its exploration. Studies show that Aspergillus is one of the pathogens that is capable of activating PANoptosis via the Z-DNA binding protein 1 (ZBP1) pathway and plays an active role in the inflammation caused by this organism.
Objective:
This article explores the nature of inflammation in ABPA and ways in which PCD could lead to novel treatment options.
Method:
PubMed was used to review the literature surrounding Aspergillus infection-related inflammation and PANoptosis.
Results:
There is evidence that apoptosis and pyroptosis protect against Aspergillus-induced inflammation, whereas necroptosis promotes inflammation.
Conclusion:
Experimental medications, in particular, necroptosis inhibitors such as necrosulfonamide and necrostatin-1, should be studied for use in the treatment of ABPA.
Insights
Allergic bronchopulmonary aspergillosis (ABPA) involves inflammation from Aspergillus fumigatus. Targeting necroptosis, a cell death pathway, may offer new treatments for ABPA by reducing inflammation.
Area of Science:
- Immunology
- Cell Biology
- Pulmonology
Background:
- Allergic bronchopulmonary aspergillosis (ABPA) is a rare airway disorder impacting asthma and cystic fibrosis patients.
- Persistent inflammation from Aspergillus fumigatus exacerbates underlying conditions and causes respiratory damage.
- Current treatments include corticosteroids and antifungals to reduce inflammation.
Purpose of the Study:
- To explore inflammation in ABPA.
- To investigate programmed cell death (PCD) pathways as potential novel treatment targets for ABPA.
Main Methods:
- Literature review using PubMed.
- Focused on Aspergillus infection-related inflammation and PANoptosis.
- Examined the role of apoptosis, pyroptosis, and necroptosis in inflammation.
Main Results:
- Apoptosis and pyroptosis demonstrate protective effects against Aspergillus-induced inflammation.
- Necroptosis, however, was found to promote inflammation in the context of ABPA.
- Aspergillus activates PANoptosis via the Z-DNA binding protein 1 (ZBP1) pathway, contributing to inflammation.
Conclusions:
- Novel therapeutic strategies for ABPA may involve targeting programmed cell death pathways.
- Necroptosis inhibitors, such as necrosulfonamide and necrostatin-1, warrant further investigation for ABPA treatment.
- Understanding PANoptosis offers new avenues for exploring ABPA pathogenesis and treatment.
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