Mucosal Infection with Unmasked Candida albicans Cells Impacts Disease Progression in a Host Niche-Specific Manner

• Published in: Infection and immunity 2022-12, Vol.90 (12), p.e0034222
• Main Authors: Wagner, Andrew S, Vogel, Amanda K, Lumsdaine, Stephen W, Phillips, Elise K, Willems, Hubertine M E, Peters, Brian M, Reynolds, Todd B
• Format: Article
• Language: English
• Subjects: Animals; Candida albicans; Candidiasis - microbiology; Candidiasis, Oral; Candidiasis, Vulvovaginal - microbiology; Disease Progression; Female; Fungal and Parasitic Infections; Glucans; Male; Mice; Mycology
• ISSN: 0019-9567; 1098-5522; 1098-5522
• DOI: 10.1128/iai.00342-22

Shielding the immunogenic cell wall epitope β(1, 3)-glucan under an outer layer of mannosylated glycoproteins is an essential virulence factor deployed by Candida albicans during systemic infection. Accordingly, mutants with increased β(1, 3)-glucan exposure (unmasking) display increased immunostimulatory capabilities and attenuated virulence during systemic infection in mice. However, little work has been done to assess the impact of increased unmasking during the two most common manifestations of candidiasis, namely, oropharyngeal candidiasis (OPC) and vulvovaginal candidiasis (VVC). We have shown previously that the expression of a single hyperactive allele of the MAP3K induces unmasking via the Cek1 MAPK pathway, attenuates fungal burden, and prolongs survival during systemic infection in mice. Here, we expand on these findings and show that infection with an unmasked mutant also impacts disease progression during OPC and VVC murine infection models. Male mice sublingually infected with the mutant showed a significant reduction in tongue fungal burden at 2 days postinfection and a modest reduction at 5 days postinfection. However, we find that selection for suppressor mutants that no longer display increased unmasking occurs within the oral cavity and is likely responsible for the restoration of fungal burden trends to wild-type levels later in the infection. In the VVC infection model, no attenuation in fungal burden was observed. However, polymorphonuclear cell recruitment and interleukin-1β (IL-1β) levels within the vaginal lumen, markers of immunopathogenesis, were increased in mice infected with unmasked cells. Thus, our data suggest a niche-specific impact for unmasking on disease progression.