AUTHOR=Deerhake M. Elizabeth , Reyes Estefany Y. , Xu-Vanpala Shengjie , Shinohara Mari L. 

TITLE=Single-Cell Transcriptional Heterogeneity of Neutrophils During Acute Pulmonary Cryptococcus neoformans Infection

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.670574

DOI=10.3389/fimmu.2021.670574

ISSN=1664-3224

ABSTRACT=<p>Neutrophils are critical as the first-line defense against fungal pathogens. Yet, previous studies indicate that neutrophil function is complex during <italic>Cryptococcus neoformans (Cn)</italic> infection. To better understand the role of neutrophils in acute pulmonary cryptococcosis, we analyzed neutrophil heterogeneity by single-cell transcriptional analysis of immune cells in the lung of <italic>Cn</italic>-infected mice from a published dataset. We identified neutrophils by reference-based annotation and identified two distinct neutrophil subsets generated during acute <italic>Cn</italic> infection: A subset with an oxidative stress signature (Ox-PMN) and another with enhanced cytokine gene expression (Cyt-PMN). Based on gene regulatory network and ligand-receptor analysis, we hypothesize that Ox-PMNs interact with the fungus and generate ROS, while Cyt-PMNs are longer-lived neutrophils that indirectly respond to <italic>Cn</italic>-derived ligands and cytokines to modulate cell-cell communication with dendritic cells and alveolar macrophages. Based on the data, we hypothesized that, during <italic>in vivo</italic> fungal infection, there is a division of labor in which each activated neutrophil becomes either Ox-PMN or Cyt-PMN.</p>