The role of Toll-like receptor 9 in a murine model of Cryptococcus gattii infection

Elias Barbosa Da Silva-Junior,Debora Decote-Ricardo,Joyce Cristina Guimarães-De-Oliveira,Celio Geraldo Freire-De-Lima,Danielle De Oliveira Nascimento,Luan Firmino-Cruz,Herbert Leonel De Matos Guedes,Lycia De Brito-Gitirana,Matheus Freire-De-Lima,Jose Osvaldo Previato,Lucia Mendonça-Previato,Alexandre Morrot,Juliana Valente Rodrigues De-Medeiros

doi:10.1038/s41598-021-80959-5

Elias Barbosa Da Silva-Junior, Debora Decote-Ricardo + Show 11 more

Open Access

https://doi.org/10.1038/s41598-021-80959-5

Copy DOI

Abstract

Toll-like receptor 9 (TLR9) is crucial to the host immune response against fungi, such as Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans, but its importance in Cryptococcus gattii infection is unknown. Our study aimed to understand the role of TLR9 during the course of experimental C. gattii infection in vivo, considering that the cryptococcal DNA interaction with the receptor could contribute to host immunity even in an extremely susceptible model. We inoculated C57BL/6 (WT) and TLR9 knock-out (TLR9−/−) mice intratracheally with 104C. gattii yeast cells. TLR9−/− mice had a higher mortality rate compared to WT mice and more yeast cells that had abnormal size, known as titan cells, in the lungs. TLR9−/− mice also had a greater number of CFUs in the spleen and brain than WT mice, in addition to having lower levels of IFN-γ and IL-17 in the lung. With these markers of aggressive cryptococcosis, we can state that TLR9−/− mice are more susceptible to C. gattii, probably due to a mechanism associated with the decrease of a Th1 and Th17-type immune response that promotes the formation of titan cells in the lungs. Therefore, our results indicate the participation of TLR9 in murine resistance to C. gattii infection.

Highlights

Toll-like receptor 9 (TLR9) is crucial to the host immune response against fungi, such as Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans, but its importance in Cryptococcus gattii infection is unknown
Our findings reveal that TLR9 is important for the survival of C57BL/6 (WT) mice infected with 104 yeast cells of C. gattii
TLR9−/− mice are more susceptible to C. gattii infection than We inoculated C57BL/6 (WT) mice

Summary

Introduction

Toll-like receptor 9 (TLR9) is crucial to the host immune response against fungi, such as Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans, but its importance in Cryptococcus gattii infection is unknown. TLR9−/− mice had a greater number of CFUs in the spleen and brain than WT mice, in addition to having lower levels of IFN-γ and IL-17 in the lung With these markers of aggressive cryptococcosis, we can state that TLR9−/− mice are more susceptible to C. gattii, probably due to a mechanism associated with the decrease of a Th1 and Th17-type immune response that promotes the formation of titan cells in the lungs. The disease can occur after inhalation of infectious forms of the fungus, which can be basidiospores or desiccated yeast cells, carried through the air that become deposited in the pulmonary alveolus This is considered a primary pulmonary infection, which may lead to a disseminated infection[17]. The spread of Cryptococcus to the CNS leads to the development of cryptococcal meningitis, described as the principal cause of mortality during infections by C. gattii[3,21]

Objectives

Methods

Results

Conclusion