Abstract
Candida albicans is a human opportunist pathogen that can grow as yeast, pseudohyphae, or true hyphae in vitro and in vivo, depending on environmental conditions. Reversible cellular morphogenesis is an important virulence factor that facilitates invasion of host tissues, escape from phagocytes, and dissemination in the blood stream. The innate immune system is the first line of defense against C. albicans infections and is influenced by recognition of wall components that vary in composition in different morphological forms. However, the relationship between cellular morphogenesis and immune recognition of this fungus is not fully understood. We therefore studied various vegetative cell types of C. albicans, singly and in combination, to assess the consequences of cellular morphogenesis on selected immune cytokine outputs from human monocytes. Hyphae stimulated proportionally lower levels of certain cytokines from monocytes per unit of cell surface area than yeast cells, but did not suppress cytokine response when copresented with yeast cells. Pseudohyphal cells induced intermediate cytokine responses. Yeast monomorphic mutants had elevated cytokine responses under conditions that otherwise supported filamentous growth and mutants of yeast and hyphal cells that were defective in cell wall mannosylation or lacking certain hypha-specific cell wall proteins could variably unmask or deplete the surface of immunostimulatory ligands. These observations underline the critical importance of C. albicans morphology and morphology-associated changes in the cell wall composition that affect both immune recognition and pathogenesis.
Highlights
Fungal pathogens are associated with a wide range of human diseases from superficial infections of the skin and mucosal surfaces to life-threatening systemic infections, depending on host health and immunocompetence
We used the cytokine response of human peripheral blood mononuclear cells (PBMCs) as a read out to investigate the role of C. albicans morphogenesis on immune recognition
The cytokine profile of human PBMCs was compared when these immune cells were exposed to yeast cells and filamentous forms of C. albicans
Summary
Fungal pathogens are associated with a wide range of human diseases from superficial infections of the skin and mucosal surfaces to life-threatening systemic infections, depending on host health and immunocompetence. Candida species account collectively for as many as 400,000 cases of systemic fungal disease with associated mortality rates of up to 40% [1,2,3,4]. Of these species, Candida albicans is the most common agent of disease and is characterized by its morphological plasticity. Candida Morphogenesis and Immune Response or parallel-sided hyphal cells [5,6,7,8,9,10]. We set out to characterize differences in the immune response by human peripheral blood mononuclear cells (PBMCs) to yeast cells, hyphae, and pseudohyphae as the three major morphological forms of C. albicans
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