AUTHOR=Tisdale-Macioce Nikeya , Green Jenna , Perl Anne-Karina T. , Ashbaugh Alan , Wiederhold Nathan P. , Patterson Thomas F. , Cushion Melanie T. 

TITLE=The Promise of Lung Organoids for Growth and Investigation of Pneumocystis Species

JOURNAL=Frontiers in Fungal Biology

VOLUME=2

YEAR=2021

URL=https://www.frontiersin.org/journals/fungal-biology/articles/10.3389/ffunb.2021.740845

DOI=10.3389/ffunb.2021.740845

ISSN=2673-6128

ABSTRACT=<p><italic>Pneumocystis</italic> species (spp.) are host-obligate fungal parasites that colonize and propagate almost exclusively in the alveolar lumen within the lungs of mammals where they can cause a lethal pneumonia. The emergence of this pneumonia in non-HIV infected persons caused by <italic>Pneumocystis jirovecii</italic> (PjP), illustrates the continued importance of and the need to understand its associated pathologies and to develop new therapies and preventative strategies. In the proposed life cycle, <italic>Pneumocystis</italic> spp. attach to alveolar type 1 epithelial cells (AEC1) and prevent gas exchange. This process among other mechanisms of <italic>Pneumocystis</italic> spp. pathogenesis is challenging to observe in real time due to the absence of a continuous <italic>ex vivo</italic> or <italic>in vitro</italic> culture system. The study presented here provides a proof-of-concept for the development of murine lung organoids that mimic the lung alveolar sacs expressing alveolar epithelial type 1 cells (AEC1) and alveolar type 2 epithelial cells (AEC2). Use of these 3-dimensional organoids should facilitate studies of a multitude of unanswered questions and serve as an improved means to screen new anti- PjP agents.</p>