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Survey of the Transcription Factor Responses of Mouse Lung Alveolar Macrophages to . | LitMetric

Survey of the Transcription Factor Responses of Mouse Lung Alveolar Macrophages to .

Pathogens

Thoracic Diseases Research Unit, Departments of Medicine and Biochemistry, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.

Published: May 2021

AI Article Synopsis

  • A fungal pathogen can cause severe infections in immunocompromised individuals, entering the body through inhalation and first interacting with alveolar macrophages (AMs) in the lungs.
  • The study uses a Mouse Transcription Factors RT Profiler™ PCR Array to analyze transcription factor (TF) responses in AMs during infection, revealing significant changes in TF expression that may play a role in pathogen-host interactions.
  • Results include verified upregulation of HIF-1A and downregulation of PPAR-γ, which correlate with a mouse model of pneumonia that simulates human infections, indicating the potential for these TFs to inform therapeutic strategies for pneumonia treatment in immunocompromised patients.

Article Abstract

is a fungal pathogen that can cause life-threatening infections in individuals who are immunocompromised. Acquired via inhalation, upon entering the respiratory tract, the fungi first encounter innate immune cells such as alveolar macrophages (AMs). Relatively little is known about the AM cellular responses to the organism, and particularly transcription factor (TF) profiles leading to early host responses during infection. Utilizing the Mouse Transcription Factors RT Profiler™ PCR Array, we report an initial TF survey of these macrophage and interactions. Expression levels of a panel of mouse TFs were compared between unstimulated and -stimulated AMs. Interestingly, a number of TFs previously implicated in pathogen-host cell interactions were highly up- or downregulated, including and . qPCR experiments were further conducted to verify the results of these surveyed transcripts. Furthermore, with immunoblotting, we show that HIF-1A and PPAR-γ are indeed significantly upregulated and downregulated, respectively. Lastly, and importantly, we report that in the mouse model of pneumonia (PCP), which mimics human pneumonia (PJP), qPCR analysis of lungs also mimic the initial TF profile analysis, suggesting an importance for these TFs in immunocompromised hosts with pneumonia. These data demonstrate the use of TF profiling in host AMs and organism interactions that may lead to a better understanding of the specific inflammatory responses of the host to pneumonia and may inform novel strategies for potential therapeutics.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151842PMC
http://dx.doi.org/10.3390/pathogens10050569DOI Listing

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