A comparison of the immunological potency of Burkholderia lipopolysaccharides in endotoxemic BALB/c mice

Abstract

Lipopolysaccharide is one of the virulence factors of the soil-borne pathogens Burkholderia pseudomallei, B. thailandensis, B. cenocepacia and B. multivorans, which cause septic melioidosis (often in B. pseudomallei infections but rarely in B. thailandensis infections) or cepacia syndromes (commonly in B. cenocepacia infections but rarely in B. multivorans infections). The inflammatory responses in Burkholderia LPS-induced endotoxemia were evaluated in this study. Prior to induction, the conserved structures and functions of each purified LPS were determined using electrophoretic phenotypes, the ratios of 3-hydroxytetradecanoic to 3-hydroxyhexadecanoic acid and endotoxin units. In an in vitro assay, cytokine expression of myeloid differentiation primary response gene 88 and Toll/IL-1 receptor domain containing adapter-inducing INF-β-dependent signaling-dependent signaling differed when stimulated by different LPS. Endotoxemia was induced in mice by s.c. injection as evidenced by increasing serum concentrations of 3-hydroxytetradecanoic acid and the septic prognostic markers CD62E and ICAM-1. During endotoxemia, splenic CD11b I-A , CD11b CD80 , CD11b CD86 and CD11b CD11c subpopulations increased. After induction with B. pseudomallei LPS, there were significant increases in splenic CD49b NK cells and CD14 macrophages. The inflamed CD11b CCR2 , CD11b CD31 , CD11b CD14 , resident CD11b CX CR1 and progenitor CD11b CD34 cells showed delayed increases in bone marrow. B. multivorans LPS was the most potent inducer of serum cytokines and chemokines, whereas B. cenocepacia LPS induced relatively low concentrations of the chemokines MIP-1α and MIP-1β. Endotoxin activities did not correlate with the virulence of Burkholderia strains. Thus factors other than LPS and/or other mechanisms of low activity LPS must mediate the pathogenicity of highly virulent Burkholderia strains.

Expression of cerebral serotonin related to anxiety-like behaviors in C57BL/6 offspring induced by repeated subcutaneous prenatal exposure to low-dose lipopolysaccharide

“…We found that an injection of >100 μg/Kg LPS resulted in an abortion in approximately 60–66% of the pregnant mice. Low dose (≤100 μg/Kg) of LPS induces maternal immune activation similar to that of a chronic infection or contact with environmental allergens such as dust [16, 19, 61]. Using low-dose LPS stimulation, the rate of abortion was as low as 11% in this study.…”

“…Lipopolysaccharide (LPS), a cell wall component of gram-negative bacteria, is known as an immunostimulant that elicits production of systemic inflammatory cytokines and chemokines, expansion of leukocytes in bone marrow, activation of the complement cascade, activation of the hypothalamic-pituitary adrenal (HPA) axis and enhancement of 5-HTergic and DAergic activity in the cerebrum [16–18]. In rodents, maternal immune activation through bacterial infection or exposure to allergens, usually administration of LPS, during pregnancy can produce long-lasting anxiety- and ASD-like behaviors in offspring.…”

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

“…Previous studies have shown that systemic cytokines, chemokines and cell adhesion molecules (CAMs) are robustly present in the blood in Burkholderia LPS-induced endotoxemic mice 14 . In this study, the levels of cytokines, chemokines, and CAMs were evaluated in the brain tissues in endotoxemic mice (the experimental design is shown in Fig.…”

“…However, the performance of astrocytes (GFAP signaling) or microglia (the numbers of transitioning cells) in B. cenocepacia LPS- or B. thailandensis LPS-induced brain was more active than the expression in B. pseudomallei LPS-induced brains. The fatty acid chain length and the kinds or repeated numbers of sugar moieties in lipid A, in terms of pathogens, leads to different changes in cytokines, chemokines and CAM expression and/or in the BBB measurements such as glial and endothelial activation, vascular permeability and the changes of infiltrating cells 14 , 20 – 22 . Septicemia is the most severe form of melioidosis in both human and animals 11 , 23 .…”

“…Previously, we reported that B. pseudomallei vgh07, B. thailandensis E264, B. cenocepacia BC2 and B. multivorans NKI379 LPS induced different degrees of splenic cell activation and bone marrow cell proliferation as well as serum cytokine (TNF-α, IL-1β, IL-6 and IL-17) and chemokine (MCP-1, MIP-1α and RANTES) expression 14 . B. multivorans LPS was a potentially stronger stimulant that induced serum inflammatory cytokine production, but B. thailandensis LPS was a weaker inducer of the expression of some factors than were other types of Burkholderia LPS 14 . Thus, we suspected that there was distinct damage to BBB permeability and/or that endothelial activation occurred in the endotoxemic brains.…”