Journal Article

An integrated model of the recognition of Candida albicans by the innate immune system

Gow, Neil A. R., Kullberg, Bart Jan, Brown, Gordon D., Netea, Mihai G.

2008

Overview

Key Points Recognition of fungi by the innate immune system depends on 'tasting' several pathogen-associated molecular patterns (PAMPs) in the fungal cell wall. Specific receptor systems have evolved for the recognition of the major polysaccharide cell wall components, such as the mannose receptor (MR) and DC-SIGN for recognition of branched N -linked mannan, Toll-like receptor 4 (TLR4) for linear O -linked mannan, galectin 3 for β-mannosides, complement receptor 3 (CR3) for β-(1,6)-glucan, and dectin 1 and TLR2 for β-glucan and phospholipomannan. Despite overlapping and sometimes redundant functions, each ligand–receptor system activates specific intracellular pathways, and this has distinct consequences for the activation of the various arms of the immune response. Differential expression of the various pattern-recognition receptors (PRRs) is an important mechanism for the cell-type-specific response to fungal pathogens. The fully integrated response to a specific pathogen depends on the mosaic of PRRs and receptor complexes that is engaged. The recognition pathways might operate singly or, more likely, in combination. Co-stimulation via multiple PAMP–PRR combinations might increase both the sensitivity and the specificity of the immune recognition process. Although described here for Candida albicans , these principles of innate immune recognition can be considered as a blueprint for pattern recognition of all pathogenic microorganisms by the innate immune response. Recognition of fungi by the innate immune system depends on 'tasting' several pathogen-associated molecular patterns in the fungal cell wall. In this Review, the authors pull together the available in vitro and in vivo data to propose an integrated model for Candida albicans recognition by the innate immune system. The innate immune response was once considered to be a limited set of responses that aimed to contain an infection by primitive 'ingest and kill' mechanisms, giving the host time to mount a specific humoral and cellular immune response. In the mid-1990s, however, the discovery of Toll-like receptors heralded a revolution in our understanding of how microorganisms are recognized by the innate immune system, and how this system is activated. Several major classes of pathogen-recognition receptors have now been described, each with specific abilities to recognize conserved bacterial structures. The challenge ahead is to understand the level of complexity that underlies the response that is triggered by pathogen recognition. In this Review, we use the fungal pathogen Candida albicans as a model for the complex interaction that exists between the host pattern-recognition systems and invading microbial pathogens.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Animals / Antigens / Biomedical and Life Sciences / Candida albicans / Candida albicans - immunology / Candidiasis - immunology / Candidiasis - microbiology / Cell Wall - immunology / Chemotherapy / Dendritic cells / Fungal infections / Humans / Immune recognition / Immune response / Immune system / Immunity, Innate - immunology / Infectious Diseases / Life Sciences / Medical Microbiology / Mice / Microbiology / Microorganisms / Models, Immunological / Mortality / Parasitology / Pathogens / Physiological aspects / Properties / Proteins / Receptors, Pattern Recognition - immunology / review-article / Virology