Integrative phenotypic and transcriptomic validation of an alveolar-like macrophage model reveals early host–pathogen dynamics during Aspergillus fumigatus infection
5 affiliations
- 1Department of Internal Medicine II, University Hospital Würzburg
- 2Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute (HKI)
- 3Chair of bioinformatics, Julius-Maximilian University Würzburg (JMU)
- 4Department of Fungal Septomics, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute (HKI)
- 5Cluster of Excellence Balance of the Microverse, Friedrich-Schiller University Jena
Abstract
Primary alveolar macrophages (pAMs) are essential for the rapid clearance of conidia and maintenance of pulmonary homeostasis. However, Aspergillus fumigatus remains the leading cause of invasive pulmonary aspergillosis in immunocompromised patients, and the mechanisms governing fungal clearance versus invasion remain poorly understood. Although, pAMs can be isolated from human donors, their broader application in in vitro infection studies is limited by their low availability and technical challenges with their maintenance in culture. In this study, we successfully adapted a previously established monocyte-derived alveolar-like macrophage (ALM) model to investigate early host-pathogen interactions upon A. fumigatus challenge. Given the requirement of GM-CSF for maintaining alveolar macrophage identity and function, we included GM-CSF differentiated macrophages (GM-M), as a widely employed reference model. Primary alveolar macrophages (pAM), isolated from human lung biopsies were utilized to validate the physiological relevance of the ALM model. Combined phenotypic, transcriptomic and functional analyses demonstrated that ALMs closely resemble pAMs under both steady-state and infection conditions across multiple time points and fungal burdens. Notably, fungal dual RNA-sequencing revealed a significant upregulation of fungal virulence-associated factors during interaction with ALM, which was not observed in our GM-M co-cultures. Collectively, these findings support the use of ALMs as a robust, experimentally accessible and physiologically relevant in vitro model for investigating early A. fumigatus infection, providing new insights into host-pathogen dynamics at the alveolar interface.
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BibTeX
@article{sohnlein2026integrative,
title = {{Integrative phenotypic and transcriptomic validation of an alveolar-like macrophage model reveals early host–pathogen dynamics during Aspergillus fumigatus infection}},
author = {Jeany Söhnlein and Sascha Schäuble and Juan Prada Salcedo and Zahraa Abboud and Dalia Sheta and Kerstin Hünniger-Ast and Michelle Seif and Hermann Einsele and Thomas Dandekar and Gianni Panagiotou and Andreas Beilhack and Juergen Loeffler},
journal = {Frontiers in Microbiology},
year = {2026},
month = oct,
doi = {10.3389/fmicb.2026.1922948},
url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.1922948/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Integrative phenotypic and transcriptomic validation of an alveolar-like macrophage model reveals early host–pathogen dynamics during Aspergillus fumigatus infection
AU - Jeany Söhnlein
AU - Sascha Schäuble
AU - Juan Prada Salcedo
AU - Zahraa Abboud
AU - Dalia Sheta
AU - Kerstin Hünniger-Ast
AU - Michelle Seif
AU - Hermann Einsele
AU - Thomas Dandekar
AU - Gianni Panagiotou
AU - Andreas Beilhack
AU - Juergen Loeffler
PY - 2026
DA - 2026/10/08
JO - Frontiers in Microbiology
DO - 10.3389/fmicb.2026.1922948
UR - https://www.frontiersin.org/articles/10.3389/fmicb.2026.1922948/full
AB - Primary alveolar macrophages (pAMs) are essential for the rapid clearance of conidia and maintenance of pulmonary homeostasis. However, Aspergillus fumigatus remains the leading cause of invasive pulmonary aspergillosis in immunocompromised patients, and the mechanisms governing fungal clearance versus invasion remain poorly understood. Although, pAMs can be isolated from human donors, their broader application in in vitro infection studies is limited by their low availability and technical challenges with their maintenance in culture. In this study, we successfully adapted a previously established monocyte-derived alveolar-like macrophage (ALM) model to investigate early host-pathogen interactions upon A. fumigatus challenge. Given the requirement of GM-CSF for maintaining alveolar macrophage identity and function, we included GM-CSF differentiated macrophages (GM-M), as a widely employed reference model. Primary alveolar macrophages (pAM), isolated from human lung biopsies were utilized to validate the physiological relevance of the ALM model. Combined phenotypic, transcriptomic and functional analyses demonstrated that ALMs closely resemble pAMs under both steady-state and infection conditions across multiple time points and fungal burdens. Notably, fungal dual RNA-sequencing revealed a significant upregulation of fungal virulence-associated factors during interaction with ALM, which was not observed in our GM-M co-cultures. Collectively, these findings support the use of ALMs as a robust, experimentally accessible and physiologically relevant in vitro model for investigating early A. fumigatus infection, providing new insights into host-pathogen dynamics at the alveolar interface.
SN - 1664-302X
ER -