The absence of microbiota delays the inflammatory response to Cryptococcus gattii

Marliete Carvalho Costa, Julliana Ribeiro Alves Santos, Maira Juliana Andrade Ribeiro, Gustavo José Cota de Freitas, Rafael Wesley Bastos, Gabriella Freitas Ferreira, Aline Silva Miranda, Raquel Duque Nascimento Arifa, Patrícia Campi Santos, Flaviano dos Santos Martins, Tatiane Alves Paixão, Antonio Lúcio Teixeira, Danielle G. Souza, Daniel Assis Santos

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

The inflammatory response plays a crucial role in infectious diseases, and the intestinal microbiota is linked to maturation of the immune system. However, the association between microbiota and the response against fungal infections has not been elucidated. Our aim was to evaluate the influence of microbiota on Cryptococcus gattii infection. Germ-free (GF), conventional (CV), conventionalized (CVN-mice that received feces from conventional animals), and LPS-stimulated mice were infected with C. gattii. GF mice were more susceptible to infection, showing lower survival, higher fungal burden in the lungs and brain, increased behavioral changes, reduced levels of IFN-γ, IL-1β and IL-17, and lower NFκBp65 phosphorylation compared to CV mice. Low expression of inflammatory cytokines was associated with smaller yeast cells and polysaccharide capsules (the main virulence factor of C. gattii) in the lungs, and less tissue damage. Furthermore, macrophages from GF mice showed reduced ability to engulf, produce ROS, and kill C. gattii. Restoration of microbiota (CVN mice) or LPS administration made GF mice more responsive to infection, which was associated with increased survival and higher levels of inflammatory mediators. This study is the first to demonstrate the influence of microbiota in the host response against C. gattii.

Original languageEnglish (US)
Pages (from-to)187-195
Number of pages9
JournalInternational Journal of Medical Microbiology
Volume306
Issue number4
DOIs
StatePublished - Jun 1 2016
Externally publishedYes

Keywords

  • Cryptococcosis
  • Cryptococcus gattii
  • Germ-free mice
  • Microbiota

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)
  • Infectious Diseases

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