Staphylococcus aureus infections of the central nervous system are serious and can be fatal. S. aureus is commonly present in the nasal cavity, and after injury to the nasal epithelium it can rapidly invade the brain via the olfactory nerve. The trigeminal nerve constitutes another potential route of brain infection. The glia of these nerves, olfactory ensheathing cells (OECs) and trigeminal nerve Schwann cells (TgSCs), as well as astrocytes populating the glia limitans layer, can phagocytose bacteria. Whilst some glial responses to S. aureus have been studied, the specific responses of different glial types are unknown. Here, we compared how primary mouse OECs, TgSCs, astrocytes and microglia responded to S. aureus. All glial types internalized the bacteria within phagolysosomes, and S. aureus-conjugated BioParticles could be tracked with subtle but significant differences in time-course of phagocytosis between glial types. Live bacteria could be isolated from all glia after 24 h in culture, and microglia, OECs and TgSCs exhibited better protection against intracellular S. aureus survival than astrocytes. All glial types responded to the bacteria by cytokine secretion.
Fig: S. aureus attaching to and being internalised into OECs, TgSCs, astrocytes and microglia. Panels show primary cultures of OECs (left panels), TgSCs (second panels), astrocytes (third panels) and microglia (right panels) from S100β-DsRed mice, in which all glia express the DsRed protein. For OECs and TgSCs, red labelling shows DsRed; for astrocytes, red labelling shows GFAP (these cells express low levels of DsRed); for microglia, red labelling shows Iba-1 (these cells express low level of DsRed) and Hoechst for nucleus staining. (A–D) Control wells of the four glial types 1 h post addition of medium without bacteria and antibiotics. (E–H) At 1 h post exposure to S. aureus, bacteria had adhered to the cell surface (arrow) and internalized (arrow) within the microglia. (I–P) After 1 h, antibiotics were added, preventing survival of bacteria in the medium. (I–L) S. aureus in glia at 6 h post exposure, some bacteria were present in the processes (arrows) while larger amounts accumulated in the perinuclear region (arrows with tail). (M–P) At 24 h post exposure, most bacteria were present in the perinuclear region (arrows with tail) while some bacteria were also present in the processes (arrows). Scale bar: 20 μm.
Overall, OECs secreted the lowest level of cytokines, suggesting that these cells, despite showing strong capacity for phagocytosis, have immunomodulatory functions that can be relevant for neural repair.
Choudhury, I.N., Chacko, A., Delbaz, A. et al. Antimicrobial responses of peripheral and central nervous system glia against Staphylococcus aureus. Sci Rep 11, 10722 (2021). https://doi.org/10.1038/s41598-021-90252-0