Involvement of L-selectin expression in<i>Burkholderia pseudomallei</i>-infected monocytes invading the brain during murine melioidosis

Chen, Yao-Shen; Lin, Hsin‐Hung; Hsueh, Pei‐Tan; Ni, Wei-Fen; Liu, Pei-Ju; Chen, Pei–Shih; Chang, Hsin-Hou; Sun, Der-Shan; Chen, Ya-Lei

doi:10.1080/21505594.2016.1232239

Cited by 11 publications

(24 citation statements)

References 53 publications

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“…5c , F4,25 = 284.96; p < 0.05, Tukey’s HSD test). The CD16/32 + CD45 + cells represent circulating phagocytes, lymphoid cells, NK cells and B cells or activated microglia 11 . These cells have been reported to be capable of carrying B. pseudomallei during neurologic melioidosis 10 , 11 .…”

Section: Resultsmentioning

confidence: 99%

“…The CD16/32 + CD45 + cells represent circulating phagocytes, lymphoid cells, NK cells and B cells or activated microglia 11 . These cells have been reported to be capable of carrying B. pseudomallei during neurologic melioidosis 10 , 11 . Undetectable or very low expression of CD16 or CD45 markers are typically present in resident monocyte/microglia and in some patrolling monocytes or lymphocytes and dendritic cells as well as in non-leukocytic pericyte or astrocytes 11 , 19 .…”

Section: Resultsmentioning

confidence: 99%

“…At this time, a large amount of free B. pseudomallei was present in the blood, and the bacteria also existed in a variety of circulating CD11b leukocytes, including Ly6C monocytes, Ly6G neutrophils, F4/80 macrophages and CD19 B cells 10 . Ly6C monocytes were the predominate type of B. pseudomallei- loaded cells 10 , 11 . If the BBB is impaired to a critical degree by endotoxemia in melioidosis, the major mechanisms by which the bacteria colonize the brain are hematogenous infection or via B. pseudomallei -loaded cells, which originate directly from circulating cells or indirectly from the bone marrow, that act as a Trojan horse to enter the brain 11 .…”

Section: Introductionmentioning

confidence: 99%

“…When inhaled, B. pseudomallei can directly invade the CNS by following extensions of the olfactory and trigeminal nerves 8 , 9 . When an adoptive transfer process that mimicked a Trojan horse was used to model a hematogenous route, circulating B. pseudomallei- loaded CD11b + Ly6C + monocytes crossed cerebral endothelial cells and induced neurologic melioidosis 10 , 11 . However, B. pseudomallei is an endotoxemia- and sepsis-causing bacteria 12 .…”

Section: Introductionmentioning

confidence: 99%

“…In a murine model of melioidosis, the bacterial load successively appeared in organs from the spleen and liver to the bone marrow before ultimately reaching the brain through hematogenous infection 10 . Once septic melioidosis is established, the CD11b + CD115 + phagocytic progenitors, CD11b + CD14 + activated macrophages, CD11b + CX 3 CR1 + resident cells as well as CD11b + CD62L + , CD11b + CCR2 + and CD11b + CD31 + inflamed cells harbored numerous B. pseudomallei in the bone marrow 11 . At this time, a large amount of free B. pseudomallei was present in the blood, and the bacteria also existed in a variety of circulating CD11b leukocytes, including Ly6C monocytes, Ly6G neutrophils, F4/80 macrophages and CD19 B cells 10 .…”

Section: Introductionmentioning

confidence: 99%

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

Hsueh¹,

Lin²,

Liu³

et al. 2018

Sci Rep

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Hsueh¹,

Lin²,

Liu³

et al. 2018

Sci Rep

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CNS infection and immune privilege

2018

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Septicemic Melioidosis Detection Using Support Vector Machine with Five Immune Cell Types

Lian

Quan

et al. 2021

Disease Markers

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Melioidosis, caused by Burkholderia pseudomallei (B. pseudomallei), predominantly occurs in the tropical regions. Of various types of melioidosis, septicemic melioidosis is the most lethal one with a mortality rate of 40%. Early detection of the disease is paramount for the better chances of cure. In this study, we developed a novel approach for septicemic melioidosis detection, using a machine learning technique—support vector machine (SVM). Several SVM models were built, and 19 features characterized by the corresponding immune cell types were generated by Cell type Identification Estimating Relative Subsets Of RNA Transcripts (CIBERSORT). Using these features, we trained a binomial SVM model on the training set and evaluated it on the independent testing set. Our findings indicated that this model performed well with means of sensitivity and specificity up to 0.962 and 0.979, respectively. Meanwhile, the receiver operating characteristic (ROC) curve analysis gave area under curves (AUCs) ranging from 0.952 to 1.000. Furthermore, we found that a concise SVM model, built upon a combination of CD8+ T cells, resting CD4+ memory T cells, monocytes, M2 macrophages, and activated mast cells, worked perfectly on the detection of septicemic melioidosis. Our data showed that its mean of sensitivity was up to 0.976 while that of specificity up to 0.993. In addition, the ROC curve analysis gave AUC close to 1.000. Taken together, this SVM model is a robust classification tool and may serve as a complementary diagnostic technique to septicemic melioidosis.

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Involvement of L-selectin expression inBurkholderia pseudomallei-infected monocytes invading the brain during murine melioidosis

Cited by 11 publications

References 53 publications

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

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

CNS infection and immune privilege

Septicemic Melioidosis Detection Using Support Vector Machine with Five Immune Cell Types

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