The hypervirulent Type-1/Type-17 phenotype of clinical isolates is specific to A/J mice.

is a fungal pathogen that causes cryptococcal meningitis in immunocompromised individuals. Both host- and pathogen-specific factors are known to affect patient outcome, and recent studies showed that strain-specific differences in clinical isolates can influence virulence in A/J mice. However, it is unclear how the immunologic and genetic background of inbred mouse strains affects disease outcome during infection.

Pulmonary granuloma formation during latent infection in C3HeB/FeJ mice involves progression through three immunological phases.

is a fungal pathogen that can cause lethal disease in immunocompromised patients. Immunocompetent host immune responses, such as formation of pulmonary granulomas, control the infection and prevent disseminated disease. Little is known about the immunological conditions establishing the latent infection granuloma in the lungs.

Pulmonary granuloma formation during latent infection in C3HeB/FeJ mice involves progression through three immunological phases.

Unlabelled: is a fungal pathogen that can cause lethal disease in immunocompromised patients. Immunocompetent host immune responses, such as formation of pulmonary granulomas, control the infection and prevent disseminated disease. Little is known about the immunological conditions establishing the latent infection granuloma in the lungs.

Single nucleotide polymorphisms are associated with strain-specific virulence differences among clinical isolates of Cryptococcus neoformans.

Studies across various pathogens highlight the importance of pathogen genetic differences in disease manifestation. In the human fungal pathogen Cryptococcus neoformans, sequence type (ST) associates with patient outcome. We performed a meta-analysis of four genomic studies and identified overlapping gene regions associated with virulence, suggesting the importance of these gene regions in cryptococcal disease in diverse clinical isolates.

Inbred Mouse Models in Research.

Animal models are frequently used as surrogates to understand human disease. In the fungal pathogen species complex, several variations of a mouse model of disease were developed that recapitulate different aspects of human disease. These mouse models have been implemented using various inbred and outbred mouse backgrounds, many of which have genetic differences that can influence host response and disease outcome.

Importance of Clinical Isolates in Research.

The human pathogenic fungus is a global health concern. Previous research in the field has focused on studies using reference strains to identify virulence factors, generate mutant libraries, define genomic structures, and perform functional studies. In this review, we discuss the benefits and drawbacks of using reference strains to study , describe how the study of clinical isolates has expanded our understanding of pathogenesis, and highlight how studies using clinical isolates can further develop our understanding of the host-pathogen interaction during infection.

Use of Clinical Isolates to Establish Criteria for a Mouse Model of Latent Infection.

The mechanisms of latency in the context of infection remain poorly understood. Two reasons for this gap in knowledge are: 1) the lack of standardized criteria for defining latent cryptococcosis in animal models and 2) limited genetic and immunological tools available for studying host parameters against in non-murine models of persistent infection. In this study, we defined criteria required for latency in infection models and used these criteria to develop a murine model of persistent infection using clinical isolates.

The Cyclin Cln1 Controls Polyploid Titan Cell Formation following a Stress-Induced G Arrest in Cryptococcus.

The pathogenic yeast Cryptococcus neoformans produces polyploid titan cells in response to the host lung environment that are critical for host adaptation and subsequent disease. We analyzed the and cell cycles to identify key aspects of the C. neoformans cell cycle that are important for the formation of titan cells.

Direct Antimicrobial Activity of IFN-β.

Type I IFNs are a cytokine family essential for antiviral defense. More recently, type I IFNs were shown to be important during bacterial infections. In this article, we show that, in addition to known cytokine functions, IFN-β is antimicrobial.