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The transcription factor Ahr1 governs the recruitment of neutrophils to the brain and clearance of Candida albicans during CNS infection
Journal article   Open access   Peer reviewed

The transcription factor Ahr1 governs the recruitment of neutrophils to the brain and clearance of Candida albicans during CNS infection

Rohan S. Wakade, Norma V. Solis, Laura C. Ristow, Melanie Wellington, Scott G. Filler and Damian J. Krysan
mBio, e0149226
07/20/2026
DOI: 10.1128/mbio.01492-26
PMID: 42474181
url
https://doi.org/10.1128/mbio.01492-26View
Published (Version of record) Open Access

Abstract

Candida albicans causes infections of the central nervous system in premature infants and people with primary immune deficiencies affecting the innate immune system. Compared to infections in other organs, the pathogenesis and host responses to C. albicans brain infections are understudied. However, the CARD9/NLRP3/interleukin 1 (IL-1) axis has been shown to play a central role in protecting the brain from C. albicans through the recruitment of neutrophils. In addition, Ece1/candidalysin is a key fungal trigger of this pathway in the brain. Here, we demonstrate that the transcription factor Ahr1 is also required for the activation of the NLRP3/IL-1β axis, recruitment of neutrophils, and clearance of C. albicans from the brain. In contrast to its function in vitro, Ahr1 does not govern the expression of ECE1 in infected brain tissue. While our data show that Ahr1 and Ece1 have overlapping effects on the NLRP3/IL-1 axis, we have also observed clear distinctions in their function with respect to chemokine secretion. Our data support a model in which Ahr1 is required for the first priming step of NLRP3 inflammasome assembly, leading to IL-1β production. Ece1/candidalysin, on the other hand, plays an important role in driving both the second step of NLRP3 inflammasome activation and the inflammasome-independent IL-1α-mediated responses to C. albicans brain infection.IMPORTANCECandida albicans infections of the brain can cause devastating consequences, particularly for premature infants. However, C. albicans infection of the brain has been understudied relative to other types of infection. We have found that the regulator of gene expression Ahr1 governs the expression of C. albicans factors that are recognized by the host and which drive the influx of neutrophils to the brain. This process is critical to the clearance of the fungus from the brain. Our data also suggest that these Ahr1-dependent factors are required to prime this immune response and function at a different step compared to the toxin candidalysin, a protein that is also required for the host to clear C. albicans from the brain.
 Mycology Candida Albicans Pathogenesis Central Nervous System Infections Clinical Microbiology and Infectious Diseases Eukaryotic Microbiology Fungal Cns Infections Fungal Immunity Fungal Pathogenesis Fungal Virulence Factors Fungal-Host Interactions Host-Fungal Interactions Host-Pathogen Interactions Microbial Pathogenesis and Immunology Molecular Mechanisms of Pathogenesis Pathogen-Specific Immunity Research Article

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