TY - JOUR
T1 - The absence of microbiota delays the inflammatory response to Cryptococcus gattii
AU - Costa, Marliete Carvalho
AU - Santos, Julliana Ribeiro Alves
AU - Ribeiro, Maira Juliana Andrade
AU - Freitas, Gustavo José Cota de
AU - Bastos, Rafael Wesley
AU - Ferreira, Gabriella Freitas
AU - Miranda, Aline Silva
AU - Arifa, Raquel Duque Nascimento
AU - Santos, Patrícia Campi
AU - Martins, Flaviano dos Santos
AU - Paixão, Tatiane Alves
AU - Teixeira, Antonio Lúcio
AU - Souza, Danielle G.
AU - Santos, Daniel Assis
N1 - Publisher Copyright:
© 2016 Elsevier GmbH.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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.
AB - 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.
KW - Cryptococcosis
KW - Cryptococcus gattii
KW - Germ-free mice
KW - Microbiota
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U2 - 10.1016/j.ijmm.2016.03.010
DO - 10.1016/j.ijmm.2016.03.010
M3 - Article
C2 - 27083265
AN - SCOPUS:84964335175
SN - 1438-4221
VL - 306
SP - 187
EP - 195
JO - International Journal of Medical Microbiology
JF - International Journal of Medical Microbiology
IS - 4
ER -