Influenza A Virus as a Predisposing Factor for Cryptococcosis

Area of Science:

• Immunology
• Infectious Diseases
• Mycology

Background:

• Influenza A virus (IAV) causes millions of infections annually, increasing susceptibility to secondary bacterial infections.
• Cryptococcus gattii fungal infections can lead to pulmonary disease and meningoencephalitis, with pre-existing lung conditions being a risk factor.
• The impact of concurrent IAV infection on C. gattii pathogenesis was previously unstudied.

Purpose of the Study:

• To investigate the effects of Influenza A H1N1 and C. gattii co-infection in a mouse model.
• To elucidate how IAV influences the host immune response during C. gattii infection.

Main Methods:

• Development of an in vivo co-infection model using Influenza A H1N1 and Cryptococcus gattii.
• Assessment of morbidity, mortality, lung pathology, and fungal burden in the brain.
• Analysis of immune cell recruitment (neutrophils, macrophages) and cytokine profiles (Type 1 interferons, IFN-γ).
• Evaluation of macrophage function, including phagocytosis, cryptococcal killing, and reactive oxygen species (ROS) production.

Main Results:

• Co-infection led to significantly increased morbidity and mortality, severe lung damage, and high fungal brain burden.
• IAV infection altered host immune responses, increasing neutrophil and macrophage recruitment to the lungs.
• IAV induced Type 1 interferons (IFN-α4/β) and reduced IFN-γ levels, potentially impairing the anti-Cryptococcus immune response.
• IAV-infected macrophages exhibited reduced phagocytosis, killing of C. gattii, and ROS production, promoting fungal proliferation.

Conclusions:

• Influenza A virus infection acts as a predisposing factor for severe disease and adverse outcomes in mice co-infected with Cryptococcus gattii.
• IAV disrupts macrophage function and alters the host immune milieu, exacerbating C. gattii pathogenesis.