STAT Immunodeficiency Disorders and Fungal Infection Susceptibility

Abstract

Invasive fungal diseases (IFD) or complicated mucocutaneous fungal infections can occur secondary to both primary and acquired immunodeficiency disorders. The signal transducer and activator of transcription (STAT) proteins are critical transcription factors involved in a wide range of processes including the immune response. This review highlights the immune pathways, clinical phenotypes and current management options of fungal infections in patient with mutations in STAT1 and STAT3, the most relevant STAT molecules involved in the host response to fungal pathogens. STAT1 gain of function (GOF) and STAT3 loss of function (LOF) (cause of autosomal dominant Hyper IgE syndrome) mutations have been associated with both chronic mucocutaneous candidiasis (CMC) and invasive fungal infections, not only inhaled moulds, mostly Aspergillus spp., but also Pneumocystis, Cryptococcus and other endemic dimorphic fungi. Significant progress has been made in the insights into the immunopathogenesis of fungal infections in these patients; nevertheless, the concrete mechanisms involved are still not fully elucidated. Early initiation of antifungal therapy followed by long-term secondary prophylaxis is normally required. Some adjunctive therapies have also been employed, although their use has not been completely established. Besides a developing knowledge in STAT1 GOF and STAT3 LOF mutations, additional research is needed. It should aim for a better understanding of the pathogenesis, diagnosis, and management of fungal infections in these patients. The identification of new therapeutic targets should help to improve patient quality of life and outcomes.