Transcriptional profile of M-NM-^TcalA and M-NM-^TcrzA Aspergillus fumigatus mutants during mammal infection
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ABSTRACT:
ORGANISM(S): Aspergillus fumigatus
SUBMITTER: Gustavo Goldman
PROVIDER: E-GEOD-27428 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Aspergillus fumigatus is a saprophytic mold capable of reaching the human deep respiratory system causing different diseases. In this study we tried to detect the virulence mechanisms developed by the fungus, using four days evolution murine intranasal infection model. For that, we develop three independent infections, in order to obtain three independent fungus samples from the lung of the infected mice per day study. Finally, we had 12 independent samples from 12 different infected mice.
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Project description:Analysis of the effect of cyclophosphamide on peripheral blood leukocyte gene expression. Certain chemotherapeutic drugs such as cyclophosphamide can enhance the antitumor efficacy of immunotherapy because of their capacity to modulate innate and adaptive immunity. Indeed, it has been argued that this capacity may be more significant to chemotherapeutic efficacy in general than is presently appreciated. To gain insights into the core mechanisms of chemoimmunotherapy, we methodically profiled the effects of cyclophosphamide on gene expression in bone marrow, spleen and peripheral blood, and on cytokine expression in plasma and bone marrow of tumor-bearing mice. Gene and protein expression were modulated early and transiently by cyclophosphamide, leading to upregulation of a variety of immunomodulatory factors, including danger signals, pattern recognition receptors, inflammatory mediators, growth factors, cytokines, chemokines and chemokine receptors. These factors are involved in sensing cyclophosphamide myelotoxicity and activating repair mechanisms, which, in turn, stimulate immunoactivation events that promote efficacy. In particular, cyclophosphamide induced a T helper 17 (Th17)-related gene signature associated with an increase in Th17, Th1 and activated CD25+CD4+Foxp3- T lymphocytes and a slight recovery of regulatory T-cells. By analyzing gene and protein expression kinetics and their relationship to the antitumor efficacy of different therapeutic schedules of combination, we determined that optimal timing for performing adoptive immunotherapy is approximately 1 day after cyclophosphamide treatment. Together, our findings highlight factors that may propel the efficacy of chemoimmunotherapy, offering a mechanistic glimpse of the important immune modulatory effects of cyclophosphamide Four-condition experiment, Untreated mice - Cyclophosphamide-treated mice 1 day - Cyclophosphamide-treated mice 2 days - Cyclophosphamide-treated mice 5 days. Biological replicates: 4, controls: 4, independently harvested. Two replicates per array.
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