Macrophages Are a Potent Source of Streptococcus-Induced IFN-β

Area of Science:

• Immunology
• Cell Biology

Background:

• Interferon-beta (IFN-β) is crucial for host defense against pathogens like Group B Streptococcus (GBS).
• Macrophages (MΦ) and dendritic cells (DC) utilize distinct pathways (cGAS-STING vs. Toll-like receptors (TLRs)) for IFN-β induction during infection.

Purpose of the Study:

• To precisely monitor phenotypic dynamics in mixed mouse MΦ/DC cultures stimulated with GBS.
• To elucidate the specific pathways involved in IFN-β induction by GBS in different myeloid cell subsets.

Main Methods:

• Utilized mixed mouse MΦ/DC cultures differentiated with GM-CSF.
• Employed transcriptional and morphological analyses to define cellular identities and phenotypes.
• Monitored IFN-β and TNF-α induction in response to GBS.

Main Results:

• Identified four mononuclear phagocyte populations, including MΦ-DC-like and transitional subsets.
• GBS induced a TLR7-dependent IFN-β signal exclusively in MΦ-like cells, independent of live bacteria.
• IFN-β induction in MΦ-like cells did not rely on the cGAS-STING pathway, unlike previously reported.
• GBS induced TNF-α independently of TLR7.
• MΦ acquired DC markers and morphology following GBS interaction, demonstrating plasticity.

Conclusions:

• IFN-β production is a key component of the anti-GBS response mediated by GM-CSF-differentiated MΦ.
• MΦ exhibit significant plasticity, adopting DC-like characteristics upon encountering GBS.
• The study clarifies distinct roles of TLR7 and cGAS-STING in IFN-β induction by GBS in MΦ versus DC.