Toll-like receptors as key mediators in innate antifungal immunity.
The Toll protein of Drosophila is a transmembrane receptor involved in dorsoventral polarization during embryonic development and recognition of infection. In mammals, Toll-like receptors (TLRs) constitute a novel protein family involved in innate immunity and respond to a wide spectrum of microorganisms, including fungi, bacteria, viruses, and protozoa. Specific agonists for nine of the ten members of the human TLR family have been described to date. TLRs as well as the TLR-associated adaptor molecule MyD88 have been implicated in the recognition of the fungal pathogens Candida albicans, Aspergillus fumigatus, Cryptococcus neoformans and Pneumocystis carinii. Moreover, several pathogen associated molecular patterns (PAMPs) located in the cell wall or cell surface of fungi have been identified as potential ligands. Yeast zymosan activates TLR2/ TLR6 heterodimers, whereas Saccharomyces cerevisiae- and C. albicans-derived mannan seems to be detected by TLR4. Phospholipomannan, present in the cell surface of C. albicans has been shown to be recognized by TLR2, while TLR4 mainly interacts with glucuronoxylomannan, the major capsular polysaccharide of C. neoformans. MyD88 has been implicated in TLR signalling of linear (1 --> 3)-beta-D-glucan, and of beta-glucan from P. carinii. These data point towards the ability of the innate immune system to utilize TLRs that are specific to different types and components of pathogenic fungi. Recent evidence further suggests that TLRs cooperate with other immune receptors involved in fungal recognition and that the selective induction of adaptor proteins finally leads to distinct signalling events upon fungal challenge.
Roeder
Alexander
A
Department of Dermatology and Allergology, Ludwig-Maximilian University, Munich, Germany.
Kirschning
Carsten J
CJ
Rupec
Rudolf A
RA
Schaller
Martin
M
Weindl
Günther
G
Korting
Hans Christian
HC
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000276:immunology; D005658:Fungi / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D008562:Membrane Glycoproteins / Q000276:immunology*; D009181:Mycoses / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology; D015398:Signal Transduction; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; C507779:MYD88 protein, human; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors