Invasive aspergillosis promotes tumor growth and severity in a tumor-bearing mouse model

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Invasive aspergillosis increases in chronic immunosuppressive diseases such as cancer. There is little information about the mechanisms by which Aspergillus infection affects the immune regulation and microenvironment of cancer cells. Hence, this study was aimed at investigating the effect of invasive aspergillosis on immunosurveillance, metastasis, and prognosis of cancer in tumor-bearing mice. After implantation of mouse mammary tumor in BALB/c mice, they were infected with Aspergillus conidia intravenously. For comparison, groups of mice were experimentally infected with Aspergillus conidia or implanted with tumor cells separately. Seven days after Aspergillus infection, the serum levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured by ELISA, and subsequently regulatory T lymphocytes were analyzed by flow cytometry. The survival of animals and mean tumor size were then determined. Our results indicated that tumor sizes in mice increased significantly after infection with Aspergillus conidia. Moreover, invasive aspergillosis enhanced the population of regulatory lymphocytes and level of TIMP-1. This study supports the idea that massive Aspergillus infection could stimulate tumor growth and increases the possibility of a bad prognosis. As a result, treatment of Aspergillus infection could be considered an important issue for efficient cancer therapy.

Les maladies immunosuppressives chroniques comme le cancer augmentent l’incidence d’aspergillose invasive. Il n’y a que peu d’informations disponibles sur les mécanismes par lesquels l’infection à Aspergillus affecte la régulation immune et le microenvironnement des cellules cancéreuses. Ainsi, cette étude visait à examiner l’effet de l’aspergillose invasive sur l’immunosurveillance, la métastase et le pronostic du cancer chez des souris porteuses de tumeurs. Après l’implantation de tumeurs mammaires chez la souris BALB/c, celles-ci ont été infectées par des conidies d’Aspergillus de façon intraveineuse. Pour fins de comparaison, des groupes de souris ont été séparément infectés par des conidies d’Aspergillus ou implantés avec des cellules tumorales. Sept jours après l’infection à Aspergillus, les niveaux sériques de TIMP-1 (tissue inhibitor of metalloproteinase-1) ont été mesurés par ELISA et les lymphocytes T régulateurs (Treg) ont été analysés subséquemment par cytométrie de flux. La survie des animaux et la taille moyenne des tumeurs ont ensuite été déterminées. Nos résultats indiquent que la taille des tumeurs des souris augmentait significativement à la suite de l’infection par les conidies d’Aspergillus. Parallèlement, l’aspergillose invasive augmentait la population de lymphocytes régulateurs et le niveau de TIMP-1. Cette étude appuie l’idée que l’infection massive par Aspergillus puisse stimuler la croissance tumorale et détériorer le pronostic. Conséquemment, le traitement de l’infection à Aspergillus devrait être considéré comme un problème important à prendre en compte pour l’efficacité de la thérapie anticancéreuse chez les patients.

Document Type: Research Article

Publication date: September 1, 2010

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  • Published since 1954, this monthly journal contains new research in the field of microbiology including applied microbiology and biotechnology; microbial structure and function; fungi and other eucaryotic protists; infection and immunity; microbial ecology; physiology, metabolism and enzymology; and virology, genetics, and molecular biology. It also publishes review articles and notes on an occasional basis, contributed by recognized scientists worldwide.
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