TY  - JOUR
AU  - Oliveira, Lorena V. N.
AU  - Costa, Marliete C.
AU  - Magalhães, Thaís F. F.
AU  - Bastos, Rafael W.
AU  - Campi Santos, Patricia
AU  - Carneiro, Hellem C. S.
AU  - Ribeiro, Noelly Q.
AU  - Ferreira, Gabriella F.
AU  - Secchim Ribeiro, Lucas
AU  - Gonçalves, Ana P. F.
AU  - Fagundes, Caio T.
AU  - Pascoal-Xavier, Marcelo A.
AU  - Djordjevic, Julianne T.
AU  - Sorrell, Tania C.
AU  - Souza, Daniele G.
AU  - Machado, Alexandre M. V.
AU  - Santos, Daniel A.
TI  - Influenza A Virus as a Predisposing Factor for Cryptococcosis
JO  - Frontiers in Cellular and Infection Microbiology
VL  - 7
SN  - 2235-2988
CY  - Lausanne
PB  - Frontiers Media
M1  - DZNE-2026-00097
SP  - 419
PY  - 2017
AB  - Influenza A virus (IAV) infects millions of people annually and predisposes to secondary bacterial infections. Inhalation of fungi within the Cryptococcus complex causes pulmonary disease with secondary meningo-encephalitis. Underlying pulmonary disease is a strong risk factor for development of C. gattii cryptococcosis though the effect of concurrent infection with IAV has not been studied. We developed an in vivo model of Influenza A H1N1 and C. gattii co-infection. Co-infection resulted in a major increase in morbidity and mortality, with severe lung damage and a high brain fungal burden when mice were infected in the acute phase of influenza multiplication. Furthermore, IAV alters the host response to C. gattii, leading to recruitment of significantly more neutrophils and macrophages into the lungs. Moreover, IAV induced the production of type 1 interferons (IFN-α4/β) and the levels of IFN-γ were significantly reduced, which can be associated with impairment of the immune response to Cryptococcus during co-infection. Phagocytosis, killing of cryptococci and production of reactive oxygen species (ROS) by IAV-infected macrophages were reduced, independent of previous IFN-γ stimulation, leading to increased proliferation of the fungus within macrophages. In conclusion, IAV infection is a predisposing factor for severe disease and adverse outcomes in mice co-infected with C. gattii.
KW  - Acetylglucosaminidase: metabolism
KW  - Animals
KW  - Behavior, Animal
KW  - Brain: microbiology
KW  - Brain: pathology
KW  - Causality
KW  - Cell Proliferation
KW  - Chemokines: metabolism
KW  - Coinfection: immunology
KW  - Coinfection: microbiology
KW  - Coinfection: mortality
KW  - Coinfection: virology
KW  - Cryptococcosis: complications
KW  - Cryptococcosis: immunology
KW  - Cryptococcus gattii: immunology
KW  - Cryptococcus gattii: pathogenicity
KW  - Cryptococcus neoformans: immunology
KW  - Cytokines: metabolism
KW  - Disease Models, Animal
KW  - Disease Susceptibility
KW  - Dogs
KW  - Female
KW  - Humans
KW  - Influenza A Virus, H1N1 Subtype: immunology
KW  - Influenza A Virus, H1N1 Subtype: pathogenicity
KW  - Interferon-gamma: metabolism
KW  - Lung: enzymology
KW  - Lung: pathology
KW  - Lung: virology
KW  - Macrophages: metabolism
KW  - Macrophages: virology
KW  - Madin Darby Canine Kidney Cells
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Neutrophils
KW  - Nitric Oxide: metabolism
KW  - Orthomyxoviridae Infections: complications
KW  - Orthomyxoviridae Infections: immunology
KW  - Peroxidase: metabolism
KW  - Peroxynitrous Acid: metabolism
KW  - Phagocytosis
KW  - Reactive Oxygen Species: metabolism
KW  - Survival Rate
KW  - Cryptococcosis (Other)
KW  - Cryptococcus gattii (Other)
KW  - co-infection (Other)
KW  - influenza A H1N1 (Other)
KW  - risk factor (Other)
KW  - Chemokines (NLM Chemicals)
KW  - Cytokines (NLM Chemicals)
KW  - IFNG protein, mouse (NLM Chemicals)
KW  - Reactive Oxygen Species (NLM Chemicals)
KW  - Peroxynitrous Acid (NLM Chemicals)
KW  - Nitric Oxide (NLM Chemicals)
KW  - Interferon-gamma (NLM Chemicals)
KW  - Peroxidase (NLM Chemicals)
KW  - Acetylglucosaminidase (NLM Chemicals)
LB  - PUB:(DE-HGF)16
DO  - DOI:10.3389/fcimb.2017.00419
UR  - https://pub.dzne.de/record/284089
ER  -