PAMPs of the Fungal Cell Wall and Mammalian PRRs
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Fungi are opportunistic pathogens that infect immunocompromised patients and are responsible for an estimated 1.5 million deaths every year. The antifungal innate immune response is mediated through the recognition of pathogen-associated molecular patterns (PAMPs) by the host’s pattern recognition receptors (PRRs). PRRs are immune receptors that ensure the internalisation and the killing of fungal pathogens. They also mount the inflammatory response, which contributes to initiate and polarise the adaptive response, controlled by lymphocytes. Both the innate and adaptive immune responses are required to control fungal infections. The immune recognition of fungal pathogen primarily occurs at the interface between the membrane of innate immune cells and the fungal cell wall, which contains a number of PAMPs. This chapter will focus on describing the main mammalian PRRs that have been shown to bind to PAMPs from the fungal cell wall of the four main fungal pathogens: Candida albicans, Aspergillus fumigatus, Cryptococcus neoformans and Pneumocystis jirovecii. We will describe these receptors, their functions and ligands to provide the reader with an overview of how the immune system recognises fungal pathogens and responds to them.
We thank the Wellcome Trust (102705) and the Medical Research Council Centre for Medical Mycology and the University of Exeter (MR/N006364/2) for funding.
All figures were made using BioRender.com.
- Aaron PA, Jamklang M, Uhrig JP et al (2018).The blood-brain barrier internalises Cryptococcus neoformans via the EphA2-tyrosine kinase receptor. Cell Microbiol 20(3)Google Scholar
- Becker KL, Aimanianda V, Wang X et al (2016) Aspergillus cell wall chitin induces anti- and proinflammatory cytokines in human pbmcs via the fc-gamma receptor/Syk/PI3K pathway. mBio 7(3)Google Scholar
- Brown GD, Denning DW, Gow NA et al (2012) Hidden killers: human fungal infections. Sci Transl Med 4(165):165rv113Google Scholar
- den Dunnen J, Gringhuis SI, Geijtenbeek TB (2009) Innate signaling by the C-type lectin DC-SIGN dictates immune responses. Cancer Immunol Immunother 58(7):1149–1157Google Scholar
- Fuchs K, Cardona Gloria Y, Wolz OO et al (2018) The fungal ligand chitin directly binds TLR2 and triggers inflammation dependent on oligomer size. EMBO Rep 19(12)Google Scholar
- Gow NAR, Latge JP Munro CA (2017) The fungal cell wall: structure, biosynthesis, and function. Microbiol Spectr 5(3)Google Scholar
- Li LY, Zhang HR, Jiang ZL et al (2018) Overexpression of dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin in dendritic cells protecting against Aspergillosis. Chin Med J (Engl) 131(21):2575–2582Google Scholar
- Lowell CA (2011). Src-family and Syk kinases in activating and inhibitory pathways in innate immune cells: signaling cross talk. Cold Spring Harb Perspect Biol 3(3)Google Scholar
- Miro MS, Rodriguez E, Vigezzi C et al (2018) Contribution of TLR2 pathway in the pathogenesis of vulvovaginal candidiasis. Pathog Dis 76(5)Google Scholar
- Skalski JH, Kottom TJ Limper AH (2015) Pathobiology of Pneumocystis pneumonia: life cycle, cell wall and cell signal transduction. FEMS Yeast Res 15(6)Google Scholar
- Smeekens SP, van de Veerdonk FL, Joosten LAB, Jacobs L, Jansen T, Williams DL, van der Meer JVM, Kullberg BJ, Netea MG (2011) The classical CD14++CD16− monocytes, but not the patrolling CD14+CD16+ monocytes, promote Th17 responses to Candida albicans. Eur J Immunol 41(10):2915–2924Google Scholar
- von Bernuth H, Picard C, Jin Z et al (2008) Pyogenic bacterial infections in humans with MyD88 deficiency. Science 321(5889):691–696Google Scholar
- Wong SSW, Aimanianda V (2017) Host Soluble Mediators: Defying the Immunological Inertness of Aspergillus fumigatus Conidia. J Fungi (Basel) 4(1)Google Scholar