January 6, 2021
Journal Article

Cryptococcus neoformans secretes small molecules that inhibit IL-1ß inflammasome-dependent secretion

Stephan De Oliveira
Pedro Bürgel
Clara Marina
Pedro Saavedra
Patrícia Albuquerque
Paulo Holanda
Raffael Castro
Heino Heyman
Carolina Coelho
Radames Cordero
Arturo Casadevall
Joshua Nosanchuk
Robin May
Aldo Tavares
Anamelia Bocca

Abstract

Cryptococcus neoformans is the agent of cryptococcal meningitis, a disease that can be life-threatening in immunocompromised hosts such as those infected with HIV. The infection thrives in hosts that poorly activate their immune system, mainly because of the yeast´s ability to survive inside macrophages and migrate towards the central nervous system. Emerging data indicate that cryptococci modulate the host immune response, but the underlying mechanisms remain largely uncharacterized. Here we show that secreted molecules from a wild-type strain of C. neoformans impair inflammatory responses driven by inflammasome activation, which in turn impact the macrophage antifungal activity. We further show that this inhibition does not involve GXM, the main constituent of the fungal capsule, but rather is partially dependent on DL-Indole-3-lactic acid (ILA), a metabolite not previously implicated in fungal virulence.

Revised: January 6, 2021 | Published: December 7, 2020

Citation

Bürgel P.H., C.L. Marina, P.H. Saavedra, P. Albuquerque, S.A. De Oliveira, P.H. Holanda, and R.A. Castro, et al. 2020. "Cryptococcus neoformans secretes small molecules that inhibit IL-1ß inflammasome-dependent secretion." Mediators of Inflammation 2020. PNNL-SA-140752. doi:10.1155/2020/3412763