Toll-like receptors: Recent advances, open questions and implications for aspergillosis control

Aspergillus fumigatus is a pathogenic mould that can cause severe and life-threatening infections in immunocompromised patients. Apart from novel and improved antifungals, additional strategies are required to protect patients at risk from developing invasive aspergillosis. Given the problems in diagnosis of this disease, important perspectives lie in attempts to elicit and strengthen a protective immunity. The innate immune system is the first line of defence against A. fumigatus. Phagocytes engulf and kill inhaled conidia, but also closely communicate with the adaptive immune system. Recognition of invading microbes is mediated by pattern recognition receptors (PRRs), and Toll-like receptors (TLR) 2 and TLR4 have been implicated in the immune response to A. fumigatus. The analysis of this process is hampered by the fact that A. fumigatus infections are inevitably coupled to germination resulting in the appearance of different fungal morphotypes, like conidia and hyphae. While conflicting data still exist on the relative importance of TLR2 and 4 in recognition of distinct A. fumigatus morphotypes, recent evidence suggests that certain TLR agonists can be used to divert the immune response towards an optimal fungicidal activity in the absence of detrimental inflammatory consequences