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Streptococci Engage TLR13 on Myeloid Cells in a Site-Specific Fashion
Julia Kolter1, Reinhild Feuerstein1, Evelyne Spoeri2
1Center for Chronic Immunodeficiency, Medical Center, University of Freiburg, 79106 Freiburg, Germany; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany;
Abstract:
Streptococci are common human colonizers with a species-specific mucocutaneous distribution. At the same time, they are among the most important and most virulent invasive bacterial pathogens. Thus, site-specific cellular innate immunity, which is predominantly executed by resident and invading myeloid cells, has to be adapted with respect to streptococcal sensing, handling, and response. In this article, we show that TLR13 is the critical mouse macrophage (MΦ) receptor in the response to group B Streptococcus, both in bone marrow-derived MΦs and in mature tissue MΦs, such as those residing in the lamina propria of the colon and the dermis, as well as in microglia. In contrast, TLR13 and its chaperone UNC-93B are dispensable for a potent cytokine response of blood monocytes to group B Streptococcus, although monocytes serve as the key progenitors of intestinal and dermal MΦs. Furthermore, a specific role for TLR13 with respect to MΦ function is supported by the response to staphylococci, where TLR13 and UNC-93B limit the cytokine response in bone marrow-derived MΦs and microglia, but not in dermal MΦs. In summary, TLR13 is a critical and site-specific receptor in the single MΦ response to β-hemolytic streptococci.
Insights
Toll-like receptor 13 (TLR13) is crucial for macrophages to detect group B Streptococcus. This receptor
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Streptococci are common colonizers and significant bacterial pathogens.
- Innate immunity, particularly myeloid cells, plays a key role in responding to streptococcal infections.
- Site-specific immune responses are essential for managing microbial threats.
Purpose of the Study:
- To investigate the role of Toll-like receptor 13 (TLR13) in the innate immune response to group B Streptococcus (GBS).
- To determine the site-specificity of TLR13 in mediating macrophage responses to GBS and staphylococci.
Main Methods:
- Utilized bone marrow-derived macrophages (MΦs) and mature tissue MΦs (including microglia, lamina propria MΦs, and dermal MΦs) from mice.
- Assessed cytokine responses to GBS and staphylococci in the presence or absence of TLR13 and its chaperone UNC-93B.
- Compared responses between different MΦ populations and blood monocytes.
Main Results:
- TLR13 is essential for mouse macrophage recognition and response to GBS in various tissues, including bone marrow, colon, dermis, and brain (microglia).
- TLR13 and UNC-93B are dispensable for blood monocyte cytokine responses to GBS, despite monocytes being precursors to tissue MΦs.
- TLR13 exhibits site-specific function, limiting cytokine responses to staphylococci in bone marrow MΦs and microglia, but not dermal MΦs.
Conclusions:
- TLR13 is a critical and site-specific receptor mediating macrophage responses to beta-hemolytic streptococci.
- The role of TLR13 in innate immunity against streptococci is dependent on the macrophage's tissue of origin and maturation state.
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