The Regulation and Consequences of Type-2 Helper T Cells During Pulmonary Cryptococcal Infection

Abstract

Pathogens are microbes that infect hosts and cause disease. There are many forms of pathogens, including: bacteria, viruses, parasites, and fungi. In particular, fungi are found throughout the environment, and as a result, humans are continuously exposed to these organisms. While in many cases our immune system provides protection against lethal disease, individuals with immune deficiencies are dramatically more susceptible to fungal disease. Conversely, fungal exposure causes over half of the pulmonary allergies and asthma experienced by otherwise healthy humans with normal immune function. The immune system is comprised of innate and adaptive components. The innate arm provides rapid and generalized protection to pathogen invasion, whereas the adaptive arm acquires specialized functions to combat specific microbes. T cells of the adaptive immune system express receptors that recognize molecules (i.e. antigens) uniquely produced by the pathogen. This allows T cells to mount highly potent responses against invading microbes while avoiding responses directed towards the host. T cells are particularly important in response to fungal infection. A selective elimination of T cells due to HIV infection results in more frequent and severe fungal disease. However, the allergy and asthma symptoms associated with fungal exposure in healthy individuals are also a direct result of inappropriate T cell responses. T cells come in many flavors and each T cell subset coordinates unique components of the immune response. Type-1 Helper (Th1) and Type-17 Helper (Th17) T cells generally contribute to protective anti-fungal immunity, whereas Type-2 Helper T (Th2) cells produced in response to many fungal infections positively correlate with disease severity and allergy symptoms. Another lineage of T cells, regulatory T (Treg) cells can inhibit the function of the helper T cells upon resolution of the infection. Mechanisms describing Th2 and Treg cell responses underlying fungal disease are ill defined. Thus, my thesis research aims to understand the induction, suppression, and downstream consequences of Th2 cells using a mouse model of pulmonary infection with the fungus, Cryptococcus neoformans.