Aspergillus terreus: how inoculum size and host characteristics affect its virulence.

Invasive aspergillosis is the most common filamentous fungal infection observed in immunocompromised patients [1]. Although the majority of these cases are caused by Aspergillus fumigatus, approximately 15% are due to Aspergillus terreus [1, 2]. Aspergillus terreus appears to be an emerging cause of infection at some institutions (eg, the Medical University Hospital of Innsbruck in Austria and the M. D. Anderson Cancer Center in Houston, Texas), and the endemic appearance of A. terreus has been demonstrated [3]. Overall, our clinical understanding of this historically difficult-to-treat pathogen is meager. Aspergillus terreus causes infections ranging from superficial infections to allergic bronchopulmonary aspergillosis, aspergilloma, and invasive disease in severely immunocompromised hosts [4]. Previous studies demonstrated that A. terreus infections were associated with dissemination, resulting in higher patient mortality, compared with other Aspergillus species [2, 4]. Aspergillus terreus is a common soil saprophyte and the only member of the genus Aspergillus that produces globose, heavy-walled hyaline cells laterally on the hyphae, called accessory conidia or aleurioconidia [5–7]. Accessory conidia can be produced singly or in clusters in vitro and in vivo. Identification of accessory conidia in tissues of infected patients is a strong indication that the infecting organism is A. terreus. Deak et al [6, 7] suggested that accessory conidia may play a role in the dissemination of disease, and recent data indicated that accessory conidia can induce elevated inflammatory responses in a model of pulmonary aspergillosis. A significant number of A. terreus isolates are resistant to amphotericin B, a polyene that had been the standard of care for the treatment of invasive fungal infections prior to the introduction of newer azoles [4, 8]. The exact mechanism of amphotericin B resistance has not yet been defined, but the level of catalase production in A. terreus may contribute to amphotericin B resistance [9]. The newer agents, such as voriconazole, posaconazole, and caspofungin, are associated with more-successful outcomes, compared with amphotericin B [1, 4]. There have been few animal models of A. terreus infections, but murine and rabbit pulmonary aspergillosis models showed the ability of A. terreus to produce disease [6, 10]. In this issue of the Journal, Slesiona et al report surprising results using infection models for A. terreus, reminding us that fundamental differences between A. fumigatus and A. terreus exist and that host pulmonary responses to A. terreus differ according to the immunosuppressive regimen used. To study A. terreus– mediated disease, this group developed an embryonated egg model and models using leukopenic and corticosteroidtreated mice and compared the patterns of infection and inflammation. In the murine A. terreus models of pulmonary aspergillosis, the key findings were as follows: (1) significantly (ie, 100 times) higher infectious doses were required for lethal infections, compared with A. fumigatus; and, under steroid treatment, both (2) in vivo germination was delayed and (3) an immune evasion by different cytokine secretions was observed. In addition, (4) liver toxicity was detected in A. terreus models, in contrast to A. fumigatus infections (Table 1). These results are important for understanding the immune response to A. terreus, although the reasons for such differences from A. fumigatus might only be partially explained by them. Among the most important findings of this work, the first was that the rate of A. terreus infection increased with the size of the fungal inoculum, but this inoculum effect was unaffected by host characteristics when compared with data Received 7 December 2011; accepted 12 December 2011. Correspondence: Cornelia Lass-Flörl, MD, Department of Hygiene and Medical Microbiology, Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Innsbruck, Tirol, Austria 6020 ([email protected]). The Journal of Infectious Diseases 2012;205:1192–4 The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. [email protected] DOI: 10.1093/infdis/jis185