| First Author | Feuerstein R | Year | 2019 |
| Journal | J Immunol | Volume | 203 |
| Issue | 12 | Pages | 3416-3426 |
| PubMed ID | 31732532 | Mgi Jnum | J:282207 |
| Mgi Id | MGI:6379906 | Doi | 10.4049/jimmunol.1900542 |
| Citation | Feuerstein R, et al. (2019) Macrophages Are a Potent Source of Streptococcus-Induced IFN-beta. J Immunol 203(12):3416-3426 |
| abstractText | IFN-beta 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-beta in macrophages (MPhi) 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 MPhi/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 MPhi-DC-like subsets, and two were transitional types. Notably, GBS induced a TLR7-dependent IFN-beta signal only in MPhi-like but not in DC-like cells. IFN-beta induction did not require live bacteria (i.e., the formation of cytolytic toxins), which are essential for IFN-beta induction via cGAS-STING. In contrast to IFN-beta, GBS induced TNF-alpha independently of TLR7. Subsequent to the interaction with streptococci, MPhi changed their immunophenotype and gained some typical DC markers and DC-like morphology. In summary, we identify IFN-beta formation as part of the antistreptococcal repertoire of GM-CSF differentiated MPhi in vitro and in vivo and delineate their plasticity. |
