Severe Candida spp. infections: new insights into natural immunity
Invasive infections caused by Candida spp. are associated with high mortality. Colonisation by Candida spp. and the capacity of the host to recognise them as potential pathogens are essential steps in the development of these infections. The major pathogen-associated molecular patterns of Candida are mannoproteins, glucans and chitins, which are recognised by C-type lectin pattern recognition receptors such as the mannose receptor, dectin-1 and dectin-2. By the secretion of proteases and toxins, and the formation of hyphae and biofilms, Candida spp. are able to enhance their virulence and pathogenicity. Studies in patients with relatively rare immunodeficiencies, such as dectin-1 deficiency, CARD9 deficiency, chronic mucocutaneous candidiasis, hyper-IgE/Job's syndrome and chronic granulomatous disease, have shown the role of dectin-1 and its signalling pathway, which involves interleukins 17 and 22, defensins and phagocytic cells, in defence against Candida. These studies also provide insights into how acquired risk factors for fungal infection operate, and may lead to new approaches for immunotherapy.