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Research Article

In vivo Hypoxia and a Fungal Alcohol Dehydrogenase Influence the Pathogenesis of Invasive Pulmonary Aspergillosis

  • Nora Grahl,

    Affiliation: Department of Immunology and Infectious Diseases, Montana State University, Bozeman, Montana, United States of America

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  • Srisombat Puttikamonkul,

    Affiliation: Department of Immunology and Infectious Diseases, Montana State University, Bozeman, Montana, United States of America

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  • Jeffrey M. Macdonald,

    Affiliation: Joint Department of Biomedical Engineering, University of North Carolina, Chapel Hill, and North Carolina State University, Raleigh, North Carolina, United States of America

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  • Michael P. Gamcsik,

    Affiliation: Joint Department of Biomedical Engineering, University of North Carolina, Chapel Hill, and North Carolina State University, Raleigh, North Carolina, United States of America

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  • Lisa Y. Ngo,

    Affiliation: Infectious Disease Sciences, Vaccine and Infectious Disease Division, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America

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  • Tobias M. Hohl,

    Affiliation: Infectious Disease Sciences, Vaccine and Infectious Disease Division, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America

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  • Robert A. Cramer mail

    rcramer@montana.edu

    Affiliation: Department of Immunology and Infectious Diseases, Montana State University, Bozeman, Montana, United States of America

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  • Published: July 21, 2011
  • DOI: 10.1371/journal.ppat.1002145

Reader Comments (2)

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An interesting study...

Posted by kausikdatta on 02 Aug 2011 at 05:51 GMT

... with some intriguing observations that add to our knowledge-base of Aspergillus-host interactions. It is a good read. I have just a couple of points to make.

The authors discuss one important caveat of the study: the observation of ethanol production in only 4 of the 10 infected mice. They offer several possible reasons that may have contributed to this, such as the lack of a more sensitive method of detection, unsuitability of bronchoalveolar lavage fluid as the site of interest and so forth. It'd be of interest to see if better detection methods - which they say they are developing - improve upon these results.

Another important caveat that the authors didn't discuss (or perhaps I missed it?) lies in the model, particularly the method of immunosuppression. Corticosteroid treatment impairs the antifungal action of immune effector cells; in mice treated with a single dose of the corticosteroid Triamcinolone, it is perhaps not surprising that at day 3 post infection there was a rebound increase in inflammatory cells, led by neutrophils, which are after all the principal effectors against Aspergillus. Unfortunately, the authors didn't check cellular infiltrate status in mice immunosuppressed with cyclophosphamide which they gave at day -2 and day +3 of infection. Cyclophosphamide causes profound neutropenia - as the authors have noted - and at the given dose, the neutropenia usually lasts for 96 hours. So, by day 3, one would expect a rebound neutrophilia in these mice prior, of course, to the second dose. It would have been interesting to see the cellular composition of the infiltrates in the cyclophosphamide-treated mice. One would expect the inflammation in this case to be largely macrophage/monocyte in nature, perhaps.

Competing interests declared: I work with Aspergillus mouse models, but not in the area/focus covered by this study.