Burkholderia pseudomallei-loaded cells act as a Trojan horse to invade the brain during endotoxemia

Abstract

Neurologic melioidosis occurs in both human and animals; however, the mechanism by which the pathogen Burkholderia pseudomallei invades the central nervous system (CNS) remains unclear. B. pseudomallei-loaded Ly6C cells have been suggested as a putative portal; however, during melioidosis, lipopolysaccharide (LPS) can drive disruption of the blood-brain barrier (BBB). This study aims to test whether the Trojan horse-like mechanism occurs during endotoxemia. The expression levels of cerebral cytokines, chemokines and cell adhesion molecules; the activation of astrocytes, microglia and endothelial cells; and the increased vascular permeability and brain-infiltrating leukocytes were evaluated using B. pseudomallei, B. thailandensis, B. cenocepacia and B. multivorans LPS-induced brains. Accordingly, different degrees of BBB damage in those brains with endotoxemia were established. The B. multivorans LPS-induced brain exhibited the highest levels of disruptive BBB according to the above mediators/indicators. Into these distinct groups of endotoxemic mice, B. pseudomallei-loaded Ly6C cells or free B. pseudomallei were adoptively transferred at equal bacterial concentrations (103 CFU). The bacterial load and number of cases of meningeal neutrophil infiltration in the brains of animals treated with B. pseudomallei-loaded Ly6C cells were higher than those in brains induced by free B. pseudomallei in any of the endotoxemic groups. In particular, these results were reproducible in B. multivorans LPS-induced brains. We suggest that B. pseudomallei-loaded cells can act as a Trojan horse and are more effective than free B. pseudomallei in invading the CNS under septic or endotoxemic conditions even when there is a high degree of BBB disruption.

Gut Microbiota Dysbiosis Is Associated with Elevated Bile Acids in Parkinson’s Disease

“…Burkholderia can cause severe inflammation in immunocompromised individuals [ 41 ] and produce kynurenine and quinolinate [ 42 ], which are proinflammatory metabolites associated with symptom severity in PD [ 43 ]. Burkholderia has also been reported to infect the brain [ 44 , 45 ]. Of particular interest, Burkholderia species encode the rate-limiting enzyme for secondary bile acid synthesis (bile-acid dehydratase) [ 46 ], highlighting the fact that the appendix microbiome of PD sufferers has an enrichment of microbiota that metabolize bile acids.…”

Type VI Secretion System Accessory Protein TagAB-5 Promotes Burkholderia pseudomallei Pathogenicity in Human Microglia

“…Several studies employed animal models to investigate how B. pseudomallei causes CNS infection. Previously, a monocyte (CD11b+) was found to act as a Trojan horse carrying B. pseudomallei across the cerebral endothelium and inducing neurological melioidosis in BALB/c mice [12,20]. Other studies in BALB/C and C75B1/6 mice demonstrated that B. pseudomallei cause CNS infection by invading the olfactory nerve or trigeminal nerve [10] and crossing the blood-brain barrier [9,33].…”

“…Microglial activation results in their production of proinflammatory cytokines such as interleukin 1 (IL-1), interleukin 6 (IL-6), interleukin 8 (IL-8), and tumor necrosis factor alpha (TNF-α) [19]. During murine melioidosis, the activation and expansion of microglia have been found in the brain [20]. However, the role of microglia against B. pseudomallei infection is still unknown.…”

Bacterial capsules: Occurrence, mechanism, and function

“…According to Gendrin et al, GBS strains enhance their intracellular survival and propagation by abandoning their capsule. This mechanism does not involve concealment within macrophages (also called the “Trojan horse” mechanism 121 , 122 ). Concurrently, there is an observed increase in the permeability of the BBB associated with GBS 123 .…”