Increased serum antimicrobial peptide LL-37 and HBD-2 combined with 25-hydroxyvitamin D3 deficiency in infants with pertussis.

INTRODUCTION: Most children with serious infection diseases suffer from malnutrition. Vitamin D participates in the immune response through endogenous antimicrobial peptides (AMPs) regulation. The aim of this study is to investigate the expression of 25-hydroxyvitamin D3 [25(OH)D3], AMPs [LL-37 and human ß-defensin 2 (HBD-2)] in the children with pertussis. METHODOLOGY: Serum levels of 25(OH)D3, LL-37, and HBD-2 were detected in 116 children with pertussis aged at 1-12 months (67 males and 49 females). Fifty healthy infants at similar age were employed as normal controls. RESULTS: The serum 25(OH)D3 levels in the children with mild (27.30 ± 5.98 ng/ml) and severe (24.40 ± 6.27 ng/ml) pertussis were significantly lower than that in the healthy group (30.16 ± 5.13 ng/ml; p <0.01). The vitamin D deficiency rates in children with mild (55.9%) and severe (78.12%) pertussis were significantly higher than that in the control group (34%; p < 0.01). The serum levels of LL-37 and HBD-2 were significantly higher in pertussis patients. Spearman rank correlation analysis did not show any correlation of 25-(OH)D3 with LL-37 or HBD-2. CONCLUSIONS: Most children with pertussis had vitamin D deficiency accompanied by elevated serum LL-37 and HBD-2 levels. However, the average level of 25(OH)D3 at 26.50 ng/ml in the infants with pertussis may not affect the immuno-regulatory ability; thus, the infants with pertussis still maintained a higher level of AMPs (LL-37 and HBD-2) against pertussis infection.

The cytomegalovirus UL146 gene product vCXCL1 promotes the resistance of hepatic cells to CD8+ T cells through up-regulation of PD-L1.

The HCMV (human cytomegalovirus) encodes numerous proteins which function to evade the immune response, which allows the virus to replicate. Exploring the mechanisms of HCMV immune escape helps to find the strategy to inhibit HCMV replicate. CD8+ T cells play a critical role in the immune response to viral pathogens. However, the mechanisms of HCMV to evade the attack by CD8+ T cells remain largely unknown. Viral CXCL1 (vCXCL1) is the production of HCMV UL146 gene. Here, we found that vCXCL1 promoted the resistance of hepatic cells to CD8+ T cells. vCXCL1 increased the levels of PD-L1 protein expression and mRNA expression. VCXCL1 enhanced the binding of STAT3 transcription factor to the promoter of PD-L1 and increased the activity of PD-L1 promoter. Furthermore, down-regulation of PD-L1 reduced the effects of vCXCL1 on the resistance of hepatic cells to CD8+ T cells. Taken together, vCXCL1 promotes the resistance of hepatic cells to CD8+ T cells through up-regulation of PD-L1. This finding might provide a new mechanism of HCMV immune escape.

SAMHD1 expression is associated with low immune activation but not correlated with HIV­1 DNA levels in CD4+ T cells of patients with HIV­1.

Sterile α motif and histidine/aspartic acid domain­containing protein 1 (SAMHD1) can inhibit reverse transcription of human immunodeficiency virus­1 (HIV­1) by hydrolyzing intracellular deoxy­ribonucleoside triphosphate. However, its role in HIV­1 disease progression has not been extensively studied. To study the impacts of SAMHD1 on HIV­1 disease progression, especially on DNA levels, we investigated SAMHD1 levels in the peripheral blood of HIV­1 elite controllers (ECs), antiretroviral therapy (ART) naive viremic progressors (VPs) and patients with HIV­1 receiving ART (HIV­ARTs) compared with healthy controls. In addition, the present study analyzed the relationship between SAMHD1 and interferon­α, immune activation and HIV­1 DNA levels. The results of the present study demonstrated elevated SAMHD1 expression in the peripheral blood mononuclear cells of all patients withHIV­1, but higher SAMHD1 expression in the CD4+ T cells of only ECs compared with healthy controls. Immune activation was increased in the VPs and decreased in the ECs compared with healthy controls. Substantially lower HIV­1 DNA levels were identified in ECs compared with those in VPs and HIV­ARTs. SAMHD1 expression was associated with low levels of immune activation. No significant correlation was observed between SAMHD1 and HIV­1 DNA levels. Overall, the findings of the present study indicated that SAMHD1 was highly expressed in ECs, which may be associated with low immune activation levels, but was not directly related to HIV­1 DNA levels.

Alteration of serum high-mobility group protein 1 (HMGB1) levels in children with enterovirus 71-induced hand, foot, and mouth disease.

Hand, foot, and mouth disease (HFMD) is a common pediatric disease caused by enterovirus infection. It typically presents as a fever along with flat, discolored spots and bumps on the hands, feet, and mouth. Compared with other viruses, enterovirus 71 (EV71)-induced HFMD is more prone to cause severe complications in children, such as brainstem encephalitis, cardiopulmonary disorders, and even death. More in-depth studies are still necessary to understand the characteristics of EV71-induced HFMD, although some related research has been reported so far. High-mobility group box 1 (HMGB1) is an inflammatory cytokine that can upregulate other inflammatory factors through its receptors, such as Toll-like receptors and the receptor for advanced glycation endproducts.We prospectively investigated the alteration of serum HMGB1, interleukin (IL)-6, and tumor necrosis factor (TNF)-α levels before and after treatment in 82 children with HFMD.We found that the serum HMGB1, IL-6, and TNF-α levels were significantly increased in EV71-induced HFMD, and that these changes were more serious in the severe and critical HMFD groups; however, there was no significant difference in the HMGB1 level between the normal control and mild HMFD groups. Moreover, the serum HMGB1 level was positively correlated with the alteration of serum IL-6 and TNF-α concentrations.These results suggest that HMGB1 is involved in the inflammatory pathogenesis of EV71-induced HFMD and that the serum level of HMGB1 could be applied as a clinical indicator for the severity of HFMD, and also a sign for the recovery prognosis of HFMD.

[Effects of lentinan on interleukin-1ß-induced transdifferentiation of human embryonic lung fibroblasts to myofibroblasts].

OBJECTIVE: To study the effects of interleukin-1ß (IL-1ß) on transdifferentiation of human embryonic lung fibroblasts to myofibroblasts and the effects of lentinan on the transdifferentiation. METHODS: The human embryonic lung fibroblasts were cultured in vitro, and fibroblasts were treated with different concentrations of IL-1ß and lentinan. The proliferation activity of the human embryonic lung fibroblasts was evaluated by the Cell Counting Kit-8 (CCK-8). The expression of α-smooth muscle actin (α-SMA) protein was measured by immunocytochemistry. The levels of fibronectin (FN), typeⅠcollagen (ColⅠ) and α-SMA mRNA were detected by RT-PCR. RESULTS: Compared with the untreated control group, the absorbance value of cell proliferation, α-SMA protein levels, FN, ColⅠand α-SMA mRNA expression were significantly up-regulated after different concentrations of IL-1ß (0.1, 1, 10 ng/mL) treatment for 48 hrs (P<0.01). Lentinan treatment inhibited up-regulation of the cell proliferation activity, α-SMA protein levels, FN, ColⅠand α-SMA mRNA expression induced by IL-1ß in a dose-independent manner (P<0.01). CONCLUSIONS: Lentinan can suppress human embryonic lung fibroblast proliferation, fibroblast-myofibroblast transdifferentiation and extra cellular matrix synthesis induced by IL-1ß.