CD11b+Gr-1low cells that accumulate in M.leprae-induced granulomas of the footpad skin of nude mice have the characteristics of monocytic-myeloid-derived suppressor cells / 나학회지

CD11b+Gr-1low cells that are increased in the lungs of a Mycobacterium (M) tuberculosisinfection mouse model have the characteristics of monocytic (M) - myeloid - derived suppressor cells (MDSCs) and harbor M.tuberculosis. Interestingly, a high number of M-MDSCs have also been observed in skin lesions of patients with lepromatous leprosy.We hypothesized that CD11b+Gr-1low cells might be involved in the pathogenesis of leprosy, as they are in tuberculosis. In the current study, we investigated the issue of whether CD11b+Gr-1low cells accumulate in Mycobacterium (M) leprae-induced granulomas of the footpad skin of nude mice. Our results show that CD11b+Gr-1low cells began to accumulate in the 7-month-old M.leprae-induced granulomas and were replaced by other leukocytes, including CD11b + Gr-1 high over time during M.leprae infections. CD11b+Gr-1low cells expressed the surface markers of M-MDSC, Ly6C high and Ly6G low . In addition, CD11b+Gr-1low cells have the nuclei of a mononuclear cell type and expressed higher levels of arginase 1 (Arg1) and inducible NO synthetase (iNOS).Furthermore, they showed a higher infection rate by M.leprae. Taken together, our results indicate that the inoculation with M.leprae induced an accumulation of CD11b+Gr-1low at a relatively early stage, 7-month-old M.leprae-induced granulomas, and that CD11b+Gr-1low have the characteristics of M-MDSC and may act as a reservoir for M.leprae.

Shigella outer membrane protein PSSP-1 is broadly protective against Shigella infection.

In developing countries, Shigella is a primary cause of diarrhea in infants and young children. Although antibiotic therapy is an effective treatment for shigellosis, therapeutic options are narrowing due to the emergence of antibiotic resistance. Thus, preventive vaccination could become the most efficacious approach for controlling shigellosis. We have identified several conserved protein antigens that are shared by multiple Shigella serotypes and species. Among these, one antigen induced cross-protection against experimental shigellosis, and we have named it pan-Shigella surface protein 1 (PSSP-1). PSSP-1-induced protection requires a mucosal administration route and coadministration of an adjuvant. When PSSP-1 was administered intranasally, it induced cross-protection against Shigella flexneri serotypes 2a, 5a, and 6, Shigella boydii, Shigella sonnei, and Shigella dysenteriae serotype 1. Intradermally administered PSSP-1 induced strong serum antibody responses but failed to induce protection in the mouse lung pneumonia model. In contrast, intranasal administration elicited efficient local and systemic antibody responses and production of interleukin 17A and gamma interferon. Interestingly, blood samples from patients with recent-onset shigellosis showed variable but significant mucosal antibody responses to other conserved Shigella protein antigens but not to PSSP-1. We suggest that PSSP-1 is a promising antigen for a broadly protective vaccine against Shigella.

Ginsenoside fractions regulate the action of monocytes and their differentiation into dendritic cells.

BACKGROUND: Panax ginseng (i.e., ginseng) root is extensively used in traditional oriental medicine. It is a modern pharmaceutical reagent for preventing various human diseases such as cancer. Ginsenosides-the major active components of ginseng-exhibit immunomodulatory effects. However, the mechanism and function underlying such effects are not fully elucidated, especially in human monocytes and dendritic cells (DCs). METHODS: We investigated the immunomodulatory effect of ginsenosides from Panax ginseng root on CD14(+) monocytes purified from human adult peripheral blood mononuclear cells (PBMCs) and on their differentiation into DCs that affect CD4(+) T cell activity. RESULTS: After treatment with ginsenoside fractions, monocyte levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 increased through phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK), but not p38 mitogen-activated protein kinase (MAPK). After treatment with ginsenoside fractions, TNF-α production and phosphorylation of ERK1/2 and JNK decreased in lipopolysaccharide (LPS)-sensitized monocytes. We confirmed that DCs derived from CD14(+) monocytes in the presence of ginsenoside fractions (Gin-DCs) contained decreased levels of the costimulatory molecules CD80 and CD86. The expression of these costimulatory molecules decreased in LPS-treated DCs exposed to ginsenoside fractions, compared to their expression in LPS-treated DCs in the absence of ginsenoside fractions. Furthermore, LPS-treated Gin-DCs could not induce proliferation and interferon gamma (IFN-γ) production by CD4(+) T cells with the coculture of Gin-DCs with CD4+ T cells. CONCLUSION: These results suggest that ginsenoside fractions from the ginseng root suppress cytokine production and maturation of LPS-treated DCs and downregulate CD4(+) T cells.

Temporary postoperative visual loss associated with intracerebral hemorrhage after laparoscopic appendectomy: a case report.

Postoperative visual loss (POVL) after non-ophthalmic surgery is rare, with a reported incidence ranging from 0.013 to 0.2%. Most perioperative visual loss is associated with spine operations and cardiac bypass procedures. The most common cause of POVL is ischemic optic neuropathy. However, there are no previous reports of postoperative visual loss after laparoscopic appendectomy. A 43-year-old female with no underlying disease underwent laparoscopic appendectomy; the operation was completed in one hour and her blood pressure was stable during the perioperative period. In the post-anesthetic care unit, the patient complained of nausea and headache, but she did not complain of any unusual visual symptoms. Approximately one hour after arriving at the ward, the patient complained of visual disturbance. Neurologic examination revealed left homonymous hemianopsia, and subarachnoid hemorrhage and intracerebral hemorrhage were found in the occipital area on brain MRI.

Rifampicin Inhibits the LPS-induced Expression of Toll-like Receptor 2 via the Suppression of NF-kappaB DNA-binding Activity in RAW 264.7 Cells

Rifampicin is a macrocyclic antibiotic which is used extensively for treatment against Mycobacterium tuberculosis and other mycobacterial infections. Recently, a number of studies have focused on the immune-regulatory effects of rifampicin. Therefore, we hypothesized that rifampicin may influence the TLR2 expression in LPS-activated RAW 264.7 cells. In this study, we determined that rifampicin suppresses LPS-induced TLR2 mRNA expression. The down-regulation of TLR2 expression coincided with decreased production of TNF-alpha. Since NF-kappaB is a major transcription factor that regulates genes for TLR2 and TNF-alpha, we examined the effect of rifampicin on the LPS-induced NF-kappaB activation. Rifampicin inhibited NF-kappaB DNA-binding activity in LPS-activated RAW 264.7 cells, while it did not affect IKKalpha/beta activity. However, rifampicin slightly inhibited the nuclear translocation of NF-kappaB p65. In addition, rifampicin increased physical interaction between pregnane X receptor, a receptor for rifampicin, and NF-kappaB p65, suggesting pregnane X receptor interferes with NF-kappaB binding to DNA. Taken together, our results demonstrate that rifampicin inhibits LPS-induced TLR2 expression, at least in part, via the suppression of NF-kappaB DNA-binding activity in RAW 264.7 cells. Thus, the present results suggest that the rifampicin-mediated inhibition of TLR2 via the suppression of NF-kappaB DNA-binding activity may be a novel mechanism of the immune-suppressive effects of rifampicin.