AUTHOR=Zec Kristina , Thiebes Stephanie , Bottek Jenny , Siemes Devon , Spangenberg Philippa , Trieu Duc Viet , Kirstein Nils , Subramaniam Nirojah , Christ Robin , Klein Diana , Jendrossek Verena , Loose Maria , Wagenlehner Florian , Jablonska Jadwiga , Bracht Thilo , Sitek Barbara , Budeus Bettina , Klein-Hitpass Ludger , Theegarten Dirk , Shevchuk Olga , Engel Daniel R. TITLE=Comparative transcriptomic and proteomic signature of lung alveolar macrophages reveals the integrin CD11b as a regulatory hub during pneumococcal pneumonia infection JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1227191 DOI=10.3389/fimmu.2023.1227191 ISSN=1664-3224 ABSTRACT=Introduction

Streptococcus pneumoniae is one of the main causes of community-acquired infections in the lung alveoli in children and the elderly. Alveolar macrophages (AM) patrol alveoli in homeostasis and under infectious conditions. However, the molecular adaptations of AM upon infections with Streptococcus pneumoniae are incompletely resolved.

Methods

We used a comparative transcriptomic and proteomic approach to provide novel insights into the cellular mechanism that changes the molecular signature of AM during lung infections. Using a tandem mass spectrometry approach to murine cell-sorted AM, we revealed significant proteomic changes upon lung infection with Streptococcus pneumoniae.

Results

AM showed a strong neutrophil-associated proteomic signature, such as expression of CD11b, MPO, neutrophil gelatinases, and elastases, which was associated with phagocytosis of recruited neutrophils. Transcriptomic analysis indicated intrinsic expression of CD11b by AM. Moreover, comparative transcriptomic and proteomic profiling identified CD11b as the central molecular hub in AM, which influenced neutrophil recruitment, activation, and migration.

Discussion

In conclusion, our study provides novel insights into the intrinsic molecular adaptations of AM upon lung infection with Streptococcus pneumoniae and reveals profound alterations critical for effective antimicrobial immunity.