Streptococcus pneumoniaerapidly translocates from the nasopharynx through the cribriform plate to invade and inflame the dura

Abstract

The entry routes and translocation mechanisms of bacterial pathogens into the central nervous system remain obscure. We report here that Streptococcus pneumoniae (Sp) or polystyrene microspheres, applied to the nose of a mouse, appeared in the meninges of the dorsal cortex within minutes. Recovery of viable bacteria from dissected tissue and fluorescence microscopy showed that up to at least 72h, Sp and microspheres were predominantly in the outer of the two meninges, the pachymeninx. No Sp were found in blood or cerebrospinal fluid. Evidence that this was not an artifact of the method of administration is that in mice infected by horizontal transmission, Sp were also predominantly in the meninges and absent from blood. Intravital imaging through the skull, and flow cytometry showed recruitment and activation of LysM+ cells in the dorsal pachymeninx at 5h and 10h following intranasal infection. Imaging of the cribriform plate suggested that both Sp and microspheres entered through its foramina via an inward flow of fluid connecting the nose to the pachymeninx. Our findings bring further insight into the invasion mechanisms of bacterial pathogens such as Sp into the central nervous system, but are also pertinent to the delivery of drugs to the brain, and the entry of air-borne particles into the cranium.

Serotype 1 pneumococcus: epidemiology, genomics, and disease mechanisms

“…The S1 capsule was found to be significantly more resistant to opsonisation and complement deposition [30] with an enhanced capacity to translocate across the nasopharynx to reach the olfactory tissues and, ultimately, the brain compartments [31]. A rapid nose-to-brain translocation was reported to occur via an inward flow of fluid transporting S. pneunoniae through the cribriform plate and to the dura within minutes [32]. The hypervirulence of pneumococcal S1 was also found to be associated with the rapid release of pneumolysin and consequent enhanced dissemination [31,33].…”

“…These animal models were primarily developed using lab-adapted strains such as serotype 2 (D39) and 4 (TIGR4), or clinical isolates such as serotypes 6A, 19F, 23F, 7F, and 14. An adult murine model of pneumococcal transmission has been developed [32] which could further the understanding of factors promoting transmission of S1 and other serotypes to aid in development of better control measures.…”