PT - JOURNAL ARTICLE AU - Feuerstein, Reinhild AU - Gres, Vitka AU - Elias Perdigó, Núria AU - Baasch, Sebastian AU - Freudenhammer, Mirjam AU - Elling, Roland AU - Henneke, Philipp TI - Macrophages Are a Potent Source of <em>Streptococcus</em>-Induced IFN-β AID - 10.4049/jimmunol.1900542 DP - 2019 Dec 15 TA - The Journal of Immunology PG - 3416--3426 VI - 203 IP - 12 4099 - http://www.jimmunol.org/content/203/12/3416.short 4100 - http://www.jimmunol.org/content/203/12/3416.full SO - J. Immunol.2019 Dec 15; 203 AB - Bone marrow GM-CSF culture gives rise to four distinct populations.GM-CSF MΦ can produce IFN-β.GBS-stimulated GM-CSF MΦ have the ability to adapt their phenotype to be more DC like.IFN-β essentially modulates the host response against mucocutaneous colonizers and potential pathogens, such as group B Streptococcus (GBS). It has been reported that the dominant signaling cascade driving IFN-β in macrophages (MΦ) in streptococcal infection is the cGAS–STING pathway, whereas conventional dendritic cells (DC) exploit endosomal recognition by intracellular TLRs. In this study, we revisited this issue by precisely monitoring the phenotypic dynamics in mixed mouse MΦ/DC cultures with GM-CSF, which requires snapshot definition of cellular identities. We identified four mononuclear phagocyte populations, of which two were transcriptionally and morphologically distinct MΦ–DC-like subsets, and two were transitional types. Notably, GBS induced a TLR7-dependent IFN-β signal only in MΦ-like but not in DC-like cells. IFN-β induction did not require live bacteria (i.e., the formation of cytolytic toxins), which are essential for IFN-β induction via cGAS–STING. In contrast to IFN-β, GBS induced TNF-α independently of TLR7. Subsequent to the interaction with streptococci, MΦ changed their immunophenotype and gained some typical DC markers and DC-like morphology. In summary, we identify IFN-β formation as part of the antistreptococcal repertoire of GM-CSF differentiated MΦ in vitro and in vivo and delineate their plasticity.