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BackgroundThe failure to establish potent anti-HBV T cell responses suggests the absence of an effective innate immune activation. Kupffer cells and liver-infiltrating monocytes/macrophages have an essential role in establishing anti-HBV responses. These cells express the costimulatory molecules CD80 and CD86. CD80 expression on antigen-presenting cells (APCs) induces Th1 cell differentiation, whereas CD86 expression drives the differentiation towards a Th2 profile. The relative expression of CD80, CD86 and PD-L1 on APCs, regulates T cell activation. Few studies investigated CD80 and CD86 expression on KCs and infiltrating monocytes/macrophages in HBV-infected liver and knowledge about the expression of PD-L1 on these cells is controversial. The expression of these molecules together in CD68+ cells has not been explored in HBV-infected livers.MethodsDouble staining immunohistochemistry was applied to liver biopsies of HBV-infected and control donors to explore CD80, CD86 and PD-L1 expression in the lobular and portal areas.ResultsChronic HBV infection was associated with increased CD68+CD86+ cell count and percentage in the lobular areas, and no changes in the count and percentage of CD68+CD80+ and CD68+PD-L1+ cells, compared to the control group. While CD68+CD80+ cell count in portal areas correlated with the fibrosis score, CD68+CD80+ cell percentage in lobular areas correlated with the inflammation grade.ConclusionThe upregulation of CD86 but not CD80 and PD-L1 on CD68+ cells in HBV-infected livers, suggests that these cells do not support the induction of potent Th1. Moreover, the expression of CD80 on CD68+ cells correlates with liver inflammation and fibrosis.

The results demonstrated that the crude ethanolic extract of the Auklandia (Saussurea lappa) root plant has a wide spectrum of activity suggesting that it may be useful in the treatment of infections caused by the above clinical isolates (human pathogens).

AimThe lack of potent innate immune responses during HCV infection might lead to a delay in initiating adaptive immune responses. Kupffer cells (KCs) and liver-infiltrating monocytes/macrophages (CD68+ cells) are essential to establish effective anti-HCV responses. They express co-stimulatory molecules, CD80 and CD86. CD86 upregulation induces activator responses that are then potentially regulated by CD80. The relative levels of expression of CD80, CD86 and the inhibitory molecule, PD-L1, on CD68+ cells modulate T cell activation. A few studies have explored CD80 and PD-L1 expression on KCs and infiltrating monocytes/macrophages in HCV-infected livers, and none investigated CD86 expression in these cells. These studies have identified these cells based on morphology only. We investigated the stimulatory/inhibitory profile of CD68+ cells in HCV-infected livers based on the balance of CD80, CD86 and PD-L1 expression.MethodsCD80, CD86 and PD-L1 expression by CD68+ cells in the lobular and portal areas of the liver of chronic HCV-infected (n = 16) and control (n = 14) individuals was investigated using double staining immunohistochemistry.ResultsThe count of CD68+ KCs in the lobular areas of the HCV-infected livers was lower than that in the control (p = 0.041). The frequencies of CD68+CD80+ cells and CD68+PD-L1+ cells in both lobular and total areas of the liver were higher in HCV-infected patients compared with those in the control group (p = 0.001, 0.031 and 0.007 respectively). Moreover, in the lobular areas of the HCV-infected livers, the frequency of CD68+CD80+ cells was higher than that of CD68+CD86+ and CD68+PD-L1+ cells. In addition, the frequencies of CD68+CD80+ and CD68+CD86+ cells were higher in the lobular areas than the portal areas.ConclusionsOur results show that CD68+ cells have an inhibitory profile in the HCV-infected livers. This might help explain the delayed T cell response and viral persistence during HCV infection.

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Objective: To investigate the prevalence of Helicobacter pylori (H. pylori) infection, a crosssectional epidemiological study, based on the age and gender-specific seroprevalence of H. pylori antibodies in asymptomatic healthy Omani blood donors attending the SQUH blood bank. Methods: Analysis of the sera from 133 apparently healthy subjects, based on the serological determination of the IgM, IgG and IgA antibodies against H. pylori, was carried out using a commercially available kit ELISA (NovaLisa, NovaTec, Germany). While the presence of H. pylorispecific IgG antibodies is the marker for a "chronic" infection with this pathogen. Therefore, there was no indicator of the time of acquisition of the infection. However, the H. pylori-specific IgM antibody was a more specific marker for a recently acquired infection with H. pylori. Results: Of the 133 subjects, there were 100 (74%) males and 33 (26%) females. The age range was 15 to 50 years with a mean of 25.75依3.75 years. The overall prevalence of H. pylori infection in our study was 69.5%. The overall seroprevalence was found to be increased 69%-86% with age. Subjects between 15-20 years of age showed 71% seroprevalence, while those between 21-40 years showed gradual increase (63%-70%) with age and reached up to 87% in subjects between 41-50 years of age. A significant inverse association was found between sex and age groups. This is when each age group was examined individually; a higher positive percentage of H. pylori antibodies increasing with age was seen in males between 21-40 years of age group in comparison to the females of the same age group. Male subjects with age group between 21 to 40 years were found to have a significant seropositivity compared to the female subjects within the same group. This may reflect how frequent were the male subjects being exposed to the outer environment and their conduct than the females in this society like Oman. Conclusions: The seropositivity of H. pylori is moderately higher between ages of 21 to 30 more than any other age group.

The cytokine midkine (MK) is a growth factor that is involved in different physiological processes including tissue repair, inflammation, the development of different types of cancer and the proliferation of endothelial cells. The production of MK by primary human macrophages and monocyte-derived dendritic cells (MDDCs) was never described. We investigated whether MK is produced by primary human monocytes, macrophages and MDDCs and the capacity of macrophages and MDDCs to modulate the proliferation of endothelial cells through MK production. The TLR stimulation of human monocytes, macrophages and MDDCs induced an average of ≈200-fold increase in MK mRNA and the production of an average of 78.2, 62, 179 pg/ml MK by monocytes, macrophages and MDDCs respectively (p < 0.05). MK production was supported by its detection in CD11c+ cells, CLEC4C+ cells and CD68+ cells in biopsies of human tonsils showing reactive lymphoid follicular hyperplasia. JSH-23, which selectively inhibits NF-κB activity, decreased the TLR-induced production of MK in PMBCs, macrophages and MDDCs compared to the control (p < 0.05). The inhibition of MK production by macrophages and MDDCs using anti-MK siRNA decreased the capacity of their supernatants to stimulate the proliferation of endothelial cells (p = 0.01 and 0.04 respectively). This is the first study demonstrating that the cytokine MK is produced by primary human macrophages and MDDCs upon TLR triggering, and that these cells can stimulate endothelial cell proliferation through MK production. Our results also suggest that NF-κB plays a potential role in the production of MK in macrophages and MDDCs upon TLR stimulation. The production of MK by macrophages and MDDCs and the fact that these cells can enhance the proliferation of endothelial cells by producing MK are novel immunological phenomena that have potentially important therapeutic implications.

ZAG levels are high among Omani AIDS patients on cART and this necessitates the measurement of ZAG on routine basis, as it is associated with weight loss.