Full text loading...
Chapter 22 : Innate Recognition of Aspergillus fumigatus by the Mammalian Immune System
Category: Clinical Microbiology; Fungi and Fungal Pathogenesis
Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase
The innate immune system is responsible for the initial recognition and elimination of pathogens. Pattern recognition receptors (PRRs) appear to primarily recognize fungal cell wall components of Aspergillus fumigatus, which may only be displayed with different growth morphologies. Germination of the conidia begins with conidial swelling, progresses to germ tube formation, and ultimately results in branched, septate vegetative hyphae. Morphological changes expose these various structures, which then can act as pathogen-associated molecular patterns (PAMPs) and are recognized by specific PRRs. This chapter describes the PRRs which have been shown to recognize Aspergillus, and provides details about their role in the control this pathogen. Toll/Il-1R (TIR) domain-containing adaptor protein (TIRAP) is an adaptor protein involved specifically in bridging Toll-like receptor 4 (TLR4) and TLR2 to MyD88, resulting in NF-κB activation. Binding of pathogens by Mannose-binding lectin (MBL) results in activation of a serine protease cascade (MBL-associated serine proteases) and opsonization of the pathogen by deposition of complement components C4b and C3b. This antibody-independent activation of the classical complement cascade, known as the lectin pathway, is however not the only mode of MBL functioning. Deposition of complement leads to enhanced recognition and uptake of the fungus by phagocytes. However, A. fumigatus conidia were recently shown to bind complement regulators, including factor H, factor H-like protein 1, C4-binding protein, and plasminogen, suggesting that this pathogen has mechanisms to avoid activation of the complement system.
β-Glucan is displayed on the cell wall during specific growth morphologies of A. fumigatus. Soluble dectin-1 is able to bind to exposed β-glucan of swollen conidia (B) and germ tubes (C) but not to resting conidia (A) or hyphae (D). DIC, differential interference contrast images; Cy3, fluorescent image of soluble dectin-1 binding. Reprinted from Steele et al. (2005) with permission of the publisher.
Cartoon representation of C-type lectin receptors which recognize A. fumigatus (not drawn to scale).