Cx43-mediated hyphal folding counteracts phagosome integrity loss during fungal infection.

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.