title: The absence of microbiota delays the inflammatory response to Cryptococcus gattii.
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.
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
authors.forename: Marliete Carvalho
authors.initials: MC
authors.lastname: Costa
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
authors.forename: Julliana Ribeiro Alves
authors.initials: JR
authors.lastname: Santos
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
authors.forename: Maira Juliana Andrade
authors.initials: MJ
authors.lastname: Ribeiro
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
authors.forename: Gustavo José Cota de
authors.initials: GJ
authors.lastname: Freitas
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
authors.forename: Rafael Wesley
authors.initials: RW
authors.lastname: Bastos
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil; Departamento de Farmácia, Universidade Federal de Juiz de Fora-Campus Governador Valadares, Governador Valadares, MG 35020-220, Brazil.
authors.forename: Gabriella Freitas
authors.initials: GF
authors.lastname: Ferreira
authors.affiliation: Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG 30130-100 Brazil.
authors.forename: Aline Silva
authors.initials: AS
authors.lastname: Miranda
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
authors.forename: Raquel Duque Nascimento
authors.initials: RD
authors.lastname: Arifa
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
authors.forename: Patrícia Campi
authors.initials: PC
authors.lastname: Santos
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
authors.forename: Flaviano Dos Santos
authors.initials: Fdos S
authors.lastname: Martins
authors.affiliation: Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
authors.forename: Tatiane Alves
authors.initials: TA
authors.lastname: Paixão
authors.affiliation: Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG 30130-100 Brazil.
authors.forename: Antonio Lúcio
authors.initials: AL
authors.lastname: Teixeira
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
authors.forename: Danielle G
authors.initials: DG
authors.lastname: Souza
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil. Electronic address: das@ufmg.br.
authors.forename: Daniel Assis
authors.initials: DA
authors.lastname: Santos
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001921:Brain / Q000382:microbiology / Q000473:pathology; D015169:Colony Count, Microbial; D003453:Cryptococcosis / Q000276:immunology* / Q000473:pathology*; D056285:Cryptococcus gattii / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D005856:Germ-Free Life; D007249:Inflammation / Q000473:pathology*; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D010587:Phagocytosis; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D016019:Survival Analysis; D051316:Wiskott-Aldrich Syndrome Protein
chemical_list: D051017:Apoptosis Regulatory Proteins; C117272:Cd5l protein, mouse; D016207:Cytokines; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; C495768:Was protein, mouse; D051316:Wiskott-Aldrich Syndrome Protein
keywords: Cryptococcosis; Cryptococcus gattii; Germ-free mice; Microbiota