Streptococcus pneumoniae resists intracellular killing by olfactory ensheathing cells but not by microglia

Abstract

Olfactory ensheathing cells (OECs) are a type of specialized glial cell currently considered as having a double function in the nervous system: one regenerative, and another immune. Streptococcus pneumoniae is a major agent of severe infections in humans, including meningitis. It is commonly found in the nasopharynx of asymptomatic carriers, and, under certain still unknown conditions, can invade the brain. We evaluated whether pneumococcal cells recovered from lysed OECs and microglia are able to survive by manipulating the host cell activation. An intracellular-survival assay of S. pneumoniae in OECs showed a significant number of bacterial CFU recovered after 3 h of infection. In contrast, microglia assays resulted in a reduced number of CFU. Electron-microscopy analysis revealed a large number of pneumococci with apparently intact morphology. However, microglia cells showed endocytic vesicles containing only bacterial cell debris. Infection of OEC cultures resulted in continuous NF-κB activation. The IFN-γ-induced increase of iNOS expression was reversed in infected OECs. OECs are susceptible to S. pneumoniae infection, which can suppress their cytotoxic mechanisms in order to survive. We suggest that, in contrast to microglia, OECs might serve as safe targets for pneumococci, providing a more stable environment for evasion of the immune system.

Intranasal Borna Disease Virus (BoDV-1) Infection: Insights into Initial Steps and Potential Contagiosity

“…The importance of the OECs for infection via the olfactory route has already been shown for human herpesvirus-6 [35]. In contrast, OECs have been discussed to be an essential component of the innate immune response in order to prevent bacteria from reaching the CNS [40,41,42]. Similar observations have not been made for viral infections to date, and might be different.…”

Chlamydia muridarum Can Invade the Central Nervous System via the Olfactory and Trigeminal Nerves and Infect Peripheral Nerve Glial Cells

“…The glial cells of the olfactory nerve (OECs) are hypothesized to be the key phagocytes in this nerve, and to play key roles in the protection against microorganisms ( Harris et al., 2009 ; Panni et al., 2013 ; Nazareth et al., 2015 ). The ability to infect and survive inside OECs, rather than being phagocytosed and degraded by the cells, is thought to be a feature of microorganisms that can invade the primary olfactory nervous system ( Macedo-Ramos et al., 2016 ; Walkden et al., 2020 ). Trigeminal nerve Schwann cells (TgSCs) can also phagocytose microorganisms ( Panni et al., 2013 ), however, Schwann cells have also been shown to express lower levels of mRNA for innate immune factors ( Vincent et al., 2005 ) and to mount a far weaker immune response to bacteria ( Vincent et al., 2007 ) than OECs.…”

“…Schwann cells, however, have been shown to exhibit a significantly lower immune response to pathogens than OECs ( Vincent et al., 2007 ). Some of the bacteria that can invade the olfactory/trigeminal nerves have been shown to infect rather than be cleared by OECs/TgSCs, including S. pneumoniae ( Macedo-Ramos et al., 2016 ), B. pseudomallei ( Walkden et al., 2020 ), and N. meningitidis ( Delbaz et al., 2020 ). Thus, one possibility by which Chlamydia spp.…”

Burkholderia pseudomallei invades the olfactory nerve and bulb after epithelial injury in mice and causes the formation of multinucleated giant glial cells in vitro

“…The nasal epithelium exhibits a powerful immune defence against pathogens: the nasopharynx-associated lymphoid tissue (NALT). The NALT, which contains lymphocytes and B-/T-cell enriched zones, as well as follicle-associated epithelium with M-cells [53], constitutes the first defence against airborne pathogens [54][55][56]. Within the underlying olfactory nerve, glial cells (OECs) are efficient phagocytes, capable of engulfing both axonal debris resulting from olfactory nerve turnover and bacteria [34,40,42].…”