Cryptococcus neoformans Secretes Small Molecules That Inhibit IL-1β Inflammasome-Dependent Secretion

Joint Authors

Casadevall, Arturo
Nakayasu, Ernesto S.
Bürgel, Pedro Henrique
Marina, Clara Luna
Saavedra, Pedro H. V.
Albuquerque, Patrícia
de Oliveira, Stephan Alberto Machado
Veloso Janior, Paulo Henrique de Holanda
Castro, Raffael Araújo de
Heyman, Heino M.
Coelho, Carolina
Cordero, Radames J. B.
Nosanchuk, Joshua D.
Tavares, Aldo Henrique
Bocca, Anamelia Lorenzetti
May, Robin C.

Source

Mediators of Inflammation

Issue

Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-20, 20 p.

Publisher

Hindawi Publishing Corporation

Publication Date

2020-12-07

Country of Publication

Egypt

No. of Pages

20

Main Subjects

Diseases

Abstract EN

Cryptococcus neoformans is an encapsulated yeast that causes disease mainly in immunosuppressed hosts.

It is considered a facultative intracellular pathogen because of its capacity to survive and replicate inside phagocytes, especially macrophages.

This ability is heavily dependent on various virulence factors, particularly the glucuronoxylomannan (GXM) component of the polysaccharide capsule.

Inflammasome activation in phagocytes is usually protective against fungal infections, including cryptococcosis.

Nevertheless, recognition of C.

neoformans by inflammasome receptors requires specific changes in morphology or the opsonization of the yeast, impairing proper inflammasome function.

In this context, we analyzed the impact of molecules secreted by C.

neoformans B3501 strain and its acapsular mutant Δcap67 in inflammasome activation in an in vitro model.

Our results showed that conditioned media derived from B3501 was capable of inhibiting inflammasome-dependent events (i.e., IL-1β secretion and LDH release via pyroptosis) more strongly than conditioned media from Δcap67, regardless of GXM presence.

We also demonstrated that macrophages treated with conditioned media were less responsive against infection with the virulent strain H99, exhibiting lower rates of phagocytosis, increased fungal burdens, and enhanced vomocytosis.

Moreover, we showed that the aromatic metabolite DL-Indole-3-lactic acid (ILA) and DL-p-Hydroxyphenyllactic acid (HPLA) were present in B3501’s conditioned media and that ILA alone or with HPLA is involved in the regulation of inflammasome activation by C.

neoformans.

These results were confirmed by in vivo experiments, where exposure to conditioned media led to higher fungal burdens in Acanthamoeba castellanii culture as well as in higher fungal loads in the lungs of infected mice.

Overall, the results presented show that conditioned media from a wild-type strain can inhibit a vital recognition pathway and subsequent fungicidal functions of macrophages, contributing to fungal survival in vitro and in vivo and suggesting that secretion of aromatic metabolites, such as ILA, during cryptococcal infections fundamentally impacts pathogenesis.

American Psychological Association (APA)

Bürgel, Pedro Henrique& Marina, Clara Luna& Saavedra, Pedro H. V.& Albuquerque, Patrícia& de Oliveira, Stephan Alberto Machado& Veloso Janior, Paulo Henrique de Holanda…[et al.]. 2020. Cryptococcus neoformans Secretes Small Molecules That Inhibit IL-1β Inflammasome-Dependent Secretion. Mediators of Inflammation،Vol. 2020, no. 2020, pp.1-20.
https://search.emarefa.net/detail/BIM-1191659

Modern Language Association (MLA)

Bürgel, Pedro Henrique…[et al.]. Cryptococcus neoformans Secretes Small Molecules That Inhibit IL-1β Inflammasome-Dependent Secretion. Mediators of Inflammation No. 2020 (2020), pp.1-20.
https://search.emarefa.net/detail/BIM-1191659

American Medical Association (AMA)

Bürgel, Pedro Henrique& Marina, Clara Luna& Saavedra, Pedro H. V.& Albuquerque, Patrícia& de Oliveira, Stephan Alberto Machado& Veloso Janior, Paulo Henrique de Holanda…[et al.]. Cryptococcus neoformans Secretes Small Molecules That Inhibit IL-1β Inflammasome-Dependent Secretion. Mediators of Inflammation. 2020. Vol. 2020, no. 2020, pp.1-20.
https://search.emarefa.net/detail/BIM-1191659

Data Type

Journal Articles

Language

English

Notes

Includes bibliographical references

Record ID

BIM-1191659