Salmonella Meningitis Associated with Monocyte Infiltration in Mice

Abstract

In the current study, we examined the ability of Salmonella enterica serovar Typhimurium to infect the central nervous system and cause meningitis following the natural route of infection in mice. C57BL/6J mice are extremely susceptible to systemic infection by Salmonella Typhimurium because of loss-of-function mutations in Nramp1 (SLC11A1), a phagosomal membrane protein that controls iron export from vacuoles and inhibits Salmonella growth in macrophages. Therefore, we assessed the ability of Salmonella to disseminate to the central nervous system (CNS) after oral infection in C57BL/6J mice expressing either wild-type (resistant) or mutant (susceptible) alleles of Nramp1. In both strains, oral infection resulted in focal meningitis and ventriculitis with recruitment of inflammatory monocytes to the CNS. In susceptible Nramp1 mice, there was a direct correlation between bacteremia and the number of bacteria in the brain, which was not observed in resistant Nramp1 mice. A small percentage of Nramp1 mice developed severe ataxia, which was associated with high bacterial loads in the CNS as well as clear histopathology of necrotizing vasculitis and hemorrhage in the brain. Thus, Nramp1 is not essential for Salmonella entry into the CNS or neuroinflammation, but may influence the mechanisms of CNS entry as well as the severity of meningitis.

Salmonella Typhimurium Infection Leads to Colonization of the Mouse Brain and Is Not Completely Cured With Antibiotics

“…Recently, Bauler et al have tested the importance of host NRAMP1 in S . Typhimurium burden in the brain (Bauler et al, 2017 ).…”

ICR suckling mouse model of Zika virus infection for disease modeling and drug validation

“…To quantify the monocyte infiltration in brain tissues, the slices of brain tissues were first received immunohistochemistry (IHC) staining with anti-Ly6C antibody (Abcam), and then the degree of monocytes infiltration was digitally quantified by ImageJ software [ 45 – 47 ]. In brief, the staining patterns of Ly6C were detected by EVOS FL Cell Imaging System (Thermo Fisher Scientific), and the blot signals from the digital images were further analyzed by Image J software (NIH, USA).…”

Myeloid Cells in the Central Nervous System

“…Pathogenic invasion occurs through paracellular or transcellular routes (Coureuil et al, 2009; Konradt et al, 2016), through retro- and anterograde migration on neuronal projections, and through the ability to hijack a migratory cell (often a monocyte) in order to cross the BBB (Drevets et al, 2004). Once the trespassers have gained entry into meningeal spaces, the macrophages that reside there—as well as those in perivascular spaces—will take a particular interest in eliminating the invaders, and will thereby ultimately protect the CNS against inflammation (Bauler et al, 2017; Polfliet et al, 2001). Following this disciplinary action, the macrophages release a variety of chemoattractants into the CSF to recruit neutrophils and monocytes for additional support (Klein et al, 2017; Mildner et al, 2008).…”