Machine Learning Analysis of the Bleomycin Mouse Model Reveals the Compartmental and Temporal Inflammatory Pulmonary Fingerprint
Natalie Bordag,
Valentina Biasin,
Diana Schnoegl,
Francesco Valzano,
Katharina Jandl,
Bence M. Nagy,
Neha Sharma,
Malgorzata Wygrecka,
Grazyna Kwapiszewska,
Leigh M. Marsh
Affiliations
Natalie Bordag
Ludwig Boltzmann Institute for Lung Vascular Research, Graz 8010, Austria
Valentina Biasin
Ludwig Boltzmann Institute for Lung Vascular Research, Graz 8010, Austria; Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz 8010, Austria
Diana Schnoegl
Ludwig Boltzmann Institute for Lung Vascular Research, Graz 8010, Austria
Francesco Valzano
Ludwig Boltzmann Institute for Lung Vascular Research, Graz 8010, Austria
Katharina Jandl
Ludwig Boltzmann Institute for Lung Vascular Research, Graz 8010, Austria; Otto Loewi Research Center, Medical University of Graz, Graz 8010 Austria
Bence M. Nagy
Ludwig Boltzmann Institute for Lung Vascular Research, Graz 8010, Austria
Neha Sharma
Ludwig Boltzmann Institute for Lung Vascular Research, Graz 8010, Austria; Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz 8010, Austria
Malgorzata Wygrecka
Department of Biochemistry, Universities of Giessen and Marburg Lung Center, Giessen 35392, Germany. Member of German Center for Lung Research
Grazyna Kwapiszewska
Ludwig Boltzmann Institute for Lung Vascular Research, Graz 8010, Austria; Otto Loewi Research Center, Medical University of Graz, Graz 8010 Austria
Leigh M. Marsh
Ludwig Boltzmann Institute for Lung Vascular Research, Graz 8010, Austria; Corresponding author
Summary: The bleomycin mouse model is the extensively used model to study pulmonary fibrosis; however, the inflammatory cell kinetics and their compartmentalization is still incompletely understood. Here we assembled historical flow cytometry data, totaling 303 samples and 16 inflammatory-cell populations, and applied advanced data modeling and machine learning methods to conclusively detail these kinetics.Three days post-bleomycin, the inflammatory profile was typified by acute innate inflammation, pronounced neutrophilia, especially of SiglecF+ neutrophils, and alveolar macrophage loss. Between 14 and 21 days, rapid responders were increasingly replaced by T and B cells and monocyte-derived alveolar macrophages. Multicolour imaging revealed the spatial-temporal cell distribution and the close association of T cells with deposited collagen.Unbiased immunophenotyping and data modeling exposed the dynamic shifts in immune-cell composition over the course of bleomycin-triggered lung injury. These results and workflow provide a reference point for future investigations and can easily be applied in the analysis of other datasets.
