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Updated: Jul 16, 2025
Microfluidic Tools for Probing Fungal-Microbial Interactions at the Cellular Level
Published on: June 23, 2022
Cx43-mediated hyphal folding counteracts phagosome integrity loss during fungal infection
Beatriz Cristovao1,2, Lisa Rodrigues3, Steve Catarino1,2
1Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), Clinical Academic Centre of Coimbra (CACC), University of Coimbra , Coimbra, Portugal.
Importance:
Invasive candidiasis is a life-threatening fungal infection that can become increasingly resistant to treatment. Thus, strategies to improve immune system efficiency, such as the macrophage response during the clearance of the fungal infection, are crucial to ameliorate the current therapies. Engulfed Candida albicans, one of the most common Candida species, is able to quickly transit from yeast-to-hypha form, which can elicit a phagosomal membrane injury and ultimately lead to macrophage death. Here, we extend the understanding of phagosome membrane homeostasis during the hypha expansion and folding process. We found that loss of phagosomal membrane integrity decreases the capacity of macrophages to fold the hyphae. Furthermore, through a bioinformatic analysis, we reveal a new window of opportunities to disclose the mechanisms underlying the hyphal constraining process. We identified Cx43 as a new weapon in the armamentarium to tackle infection by potentiating hyphal folding and promoting macrophage survival.
Insights
Macrophages use membrane repair machinery and Cx43 to contain and fold growing Candida albicans hyphae, enhancing survival during infection. This study reveals Cx43
Area of Science:
- Cell Biology
- Immunology
- Mycology
Background:
- Phagolysosomes are vital for eliminating pathogens like Candida albicans.
- Maintaining phagolysosome membrane integrity is crucial during C. albicans infection as hyphae grow and damage the membrane.
- The molecular mechanisms of phagosome membrane adaptation during hyphal expansion are not fully understood.
Purpose of the Study:
- To investigate the interplay between phagosomal membrane integrity and the folding capacity of macrophages infected with C. albicans.
- To identify molecular players involved in phagosome membrane adaptation and pathogen constraint.
Main Methods:
- Analysis of RNA sequencing data from C. albicans-infected macrophages.
- Investigating the recruitment of repair machinery components to the phagolysosomal membrane.
- Assessing the role of Cx43 in phagosome dynamics and actin nucleation.
Main Results:
- Components of the membrane repair machinery are recruited to expanding phagolysosomes, and their inhibition reduces macrophage folding capacity.
- Cx43 (a gap junction protein) is recruited to expanding phagosomes and enhances the hyphal folding capacity of macrophages.
- Cx43 acts as an anchor for Arp2-mediated actin nucleation, facilitating the assembly of actin rings around hyphae-containing phagosomes.
Conclusions:
- Macrophage membrane repair mechanisms and Cx43 are critical for coping with C. albicans infection.
- Cx43 plays a novel, noncanonical role in regulating phagosome dynamics, promoting hyphal folding, and enhancing macrophage survival.
- Understanding these mechanisms offers new therapeutic strategies against invasive candidiasis.
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