Toll-like receptors (TLRs) are germline-encoded pattern recognition receptors (PRRs) that play a central role in host cell recognition and responses to virus infection, leading to the production of interferons (IFNs) and proinflammatory cytokines. In parallel, in order to establish an infection, viruses have to develop exclusively strategies to interfere with TLRs signaling, particularly some important adaptors activation such as MyD88, NF-kappaB, TRIF and IRFs, and suppress or escape host's antiviral immune response. In this paper, we review the latest findings on the various strategies used by viruses to modulate TLRs-mediated innate immune response, with special emphasis on immune evasion mechanism of VACV, HCV and HIV. By highlighting recent progress in these areas, we hope to convey a greater understanding of how viruses hamper TLRs signaling and how to overcome viral infection.
Animals ; Antiviral Agents ; pharmacology ; therapeutic use ; Humans ; Immunity, Innate ; drug effects ; Signal Transduction ; drug effects ; Toll-Like Receptors ; metabolism ; Virus Diseases ; drug therapy ; immunology ; metabolism ; pathology

Enterovirus A71 (EV-A71) causes hand, foot, and mouth disease (HFMD) and various neurological complications, including aseptic meningitis and neurogenic pulmonary edema in young children. HFMD caused by EV-A71 have broken out several times in the Asia-Pacific region since 2007. And it has been a serious threat to public health. There is no effective vaccine or antiviral drug. The pathogenesis of EV-A71 infection is unknown, and EV-A71 3C protein plays an irreplaceable role in replication and anti - innate immunity. Further research on EV-A71 3C protein is conducive to understand the pathogenesis of EV-A71 infection and antiviral drug.
Animals ; Antiviral Agents ; pharmacology ; Enterovirus ; drug effects ; immunology ; metabolism ; physiology ; Humans ; Immunity, Innate ; Viral Proteins ; chemistry ; genetics ; metabolism ; Virus Replication ; drug effects

This study examined the effect of intensive insulin therapy on immune function and inflammatory factors at the early phase after severe trauma. At day 1, 3, 5, 7 after admission, subsets of CD4(+) helper T lymphocytes (Th1/Th2) and human leukocyte antigen (HLA)-DR expression on CD14(+) monocytes were flow cytometrically measured. Levels of cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10) and other immunity markers, such as IgA, IgG, IgM, C3, C4 and C reaction protein (CRP) were examined in two groups. The results showed that TNF-α, IL-6 and CRP levels in the intensive insulin therapy group were significantly lower than those in the conventional therapy group, whereas IL-10 levels were substantially increased after intensive insulin therapy. C3 level at day 3, 5, 7 and C4 levels at day 5, 7 were lower in the intensive therapy group than in the conventional therapy group. Th1/Th2 ratios decreased gradually over time in both groups, and were much lower at day 3, 5, 7 in intensive therapy group. There were significant differences among day 3 to day 7 after admission in HLA-DR expression in CD14(+) monocytes. It was concluded that the intensive insulin therapy could decrease pro-inflammatory cytokines and increase anti-inflammatory cytokines in the elderly suffering from severe trauma, at the same time, with complement recovery being delayed. Moreover, intensive insulin therapy promoted immune suppression and, therefore, measures need be taken to address the issue.
Aged ; Aged, 80 and over ; Cytokines ; immunology ; Female ; Humans ; Hyperglycemia ; drug therapy ; immunology ; Hypoglycemic Agents ; therapeutic use ; Immunity, Innate ; drug effects ; immunology ; Immunologic Factors ; immunology ; Insulin ; therapeutic use ; Male ; Treatment Outcome ; Wounds and Injuries ; drug therapy ; immunology

Traumatic injury of the central nervous system (CNS) including brain and spinal cord remains a leading cause of morbidity and disability in the world. Delineating the mechanisms underlying the secondary and persistent injury versus the primary and transient injury has been drawing extensive attention for study during the past few decades. The sterile neuroinflammation during the secondary phase of injury has been frequently identified substrate underlying CNS injury, but as of now, no conclusive studies have determined whether this is a beneficial or detrimental role in the context of repair. Recent pioneering studies have demonstrated the key roles for the innate and adaptive immune responses in regulating sterile neuroinflammation and CNS repair. Some promising immunotherapeutic strategies have been recently developed for the treatment of CNS injury. This review updates the recent progress on elucidating the roles of the innate and adaptive immune responses in the context of CNS injury, the development and characterization of potential immunotherapeutics, as well as outstanding questions in this field.
Adaptive Immunity ; Astrocytes ; physiology ; Brain Injuries, Traumatic ; immunology ; therapy ; Histone Deacetylases ; therapeutic use ; Humans ; Immunity, Innate ; immunology ; Immunotherapy ; methods ; Inflammasomes ; drug effects ; physiology ; Macrophage Activation ; Spinal Cord Injuries ; immunology ; therapy

OBJECTIVEDiscuss the therapeutic effect of Bailing capsule and the medical gymnastics (MG) to chronic obstructive pulmonary diseases (COPD) in paracmasis.

METHODAdopt prospective study method that we divide 50 COPD patients into two group in random, the contrast group (25 patients) to treat by routine western medicine. The therapeutic group (25 patients) to treat by the Bailing capsule and the lung recovery medical gymnastics. After 6 months, we observe the patients' condition of lung ventilation, dyspneic respiration and disease resistance.

RESULTThe therapeutic group is better than the contrast group obviously, the patients' condition of dyspneic respiration are improved, the descent rate of the average level of dyspneic respiration. The therapeutic group was 24.53%, the contrast group was 3.7%. The index of lung ventilation is all improved obviously (P < 0.05 or P < 0.01). The disease resistance of the therapeutic group is improved after the treat (P < 0.01).

CONCLUSIONIt is a good method to cure COPD in paracmasis by the traditional Chinese medicine Bailing capsule and the medical gymnastics, to the patients of insufficiency of QI of the lung and kidney especially, the method can improve the disease resistance and lung ventilation.

Aged ; Capsules ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Humans ; Immunity, Innate ; drug effects ; immunology ; Male ; Middle Aged ; Physical Therapy Modalities ; Pulmonary Disease, Chronic Obstructive ; drug therapy ; immunology ; physiopathology ; therapy ; Recovery of Function ; drug effects ; Respiration ; drug effects

OBJECTIVETo investigate the effect of Am80 on innate immune response of Porphyromonas gingivalis (Pg) W83-induced periodontitis in mice.

METHODSTwenty-five mice were randomly divided into five groups, control group, PgW83-induced periodontitis group (periodontitis), Am80 (10 µg/d) treatment group (low-dose group), Am80 (50 µg/d) treatment group (middle-dose group), Am80 (100 µg/d) treatment group (high-dose group). The distance of alveolar bone resorption in each mouse was observed and measured by a dissecting microscope. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of serum anti-Pg specific IgG. The mRNA expression of interferon-γ (IFN-γ) and interleuking-12 (IL-12) in gingival tissues, draining lymph node and spleen were detected by real-time reverse transcriptase polymerase chain reaction (RT-PCR). The measurement data were statistically analyzed.

RESULTSThe resorption rate in Am80 group [(121 ± 10)%] and high-dose of Am80 group [(108 ± 8)%] was significantly different with that in periodontitis mice [(133 ± 10)% ] (P < 0.05). The serum levels of anti-Pg specific IgG of the Am80 groups of different doses (0.437 ± 0.083, 0.566 ± 0.012, and 0.386 ± 0.078) were significantly lower than that of the periodontitis group (1.151 ± 0.433) (P < 0.001). Real-time quantitative PCR assay showed that after Am80 treatment, the IL-12 mRNA levels in the gingival tissues, lymph nodes and spleen of mice were reduced to 1.107 ± 0.088, 0.806 ± 0.220, and 0.668 ± 0.756, which were all significantly different with those in periodontitis (P < 0.01). Similarly, the relative expression of IFN-γ mRNA levels in gingival tissue, lymph nodes and spleen of mice were reduced to 8.898 ± 0.427, 16.654 ± 5.995, and 1.482 ± 0.033, which were significantly different with periodontitis (P < 0.001).

CONCLUSIONSAm80 can reduce the extent of inflammation and alleviate alveolar bone resorption by modulating innate immune response.

Alveolar Bone Loss ; pathology ; Animals ; Benzoates ; pharmacology ; Gingiva ; immunology ; Immunity, Innate ; drug effects ; Immunoglobulin G ; blood ; Interferon-gamma ; genetics ; metabolism ; Interleukin-12 ; blood ; Mice ; Periodontitis ; blood ; immunology ; microbiology ; Porphyromonas gingivalis ; immunology ; RNA, Messenger ; analysis ; Random Allocation ; Spleen ; immunology ; Tetrahydronaphthalenes ; pharmacology

Conglutinin is a high molecular-weight lectin originally detected in bovine serum. It belongs to the family of collectins that bind sugar residues in a Ca(2+)-dependent manner and are effector molecules in innate immunity. Conglutinin appears to play an important role in immune defense mechanisms, showing antiviral and antibacterial activities when tested in vivo and in vitro. The present study evaluated the effect of conglutinin on the respiratory bursts in bovine peripheral phagocytes. Using nitroblue tetrazolium and hydrogen peroxide assays, we showed that sugar ligand-bound conglutinin stimulated the production of superoxide and H2O2 in granulocytes whereas the non-sugar-bound form of conglutinin inhibited these processes. These results indicate that both forms of conglutinin are able to interact with surface leukocyte receptors but have opposite effects on phagocytic activity. Our findings suggest that conglutinin bound to sugar residues on microbial surfaces can induce oxygen burst in phagocytes, and thereby mediates the elimination of pathogens and prevents the spread of infection.
Animals ; Cattle/*immunology ; Collectins/*pharmacology ; Enzyme-Linked Immunosorbent Assay/veterinary ; Female ; Granulocytes/*drug effects/immunology ; Hydrogen Peroxide/immunology ; Immunity, Innate/drug effects/immunology ; Phagocytosis/immunology ; Reactive Oxygen Species/*immunology ; Respiratory Burst/*drug effects/immunology ; Serum Globulins/*pharmacology ; Statistics, Nonparametric ; Superoxides/immunology

OBJECTIVETo explore influence of Kurarinol on specific and non-specific cell immunity in patients with chronic hepatitis B.

METHODS74 cases of CHB were randomly divided into two groups, 36 cases in treatment group, treated with 600 mg Kurarinol glucose injection, IV, once a day. After one month, Kurarinol capsule was used orally, three times a day for 2 months, 200 mg Silybin Meglumine Tablets orally, three times a day for 3 months. 38 cases in control group, only Silybin Meglumine Tablets was used, method and dosage were the same as treatment group. Compare HBV specific CTL, non-specific CTL, sub-group of T cells, changes of Th1 and Th2, negative conversion rate of HBV DNA and HBeAg of the two groups.

RESULTSIn treatment group, 3 months after treatment with Kurarinol, HBV specific CTL is higher than that before treatment (P < 0.01), it is also higher than that of control after treatment, P < 0.05) . Non-specific CTL is higher than that before treatment (P < 0.05), it is also higher than that of control after treatment (P < 0.01). CD4 is higher than that before treatment (P <0.05), it is also higher than that of control after treatment (P < 0.01), Thl is higher than that before treatment (P < 0.05), it is also higher than that of control after treatment (P < 0.01) . Negative conversion of HBV DNA and HBeAg is higher than that of control (P < 0.01).

CONCLUSIONKurarinol can improve specific and non-specific cell immunity in patients with CHB. It is one of the mechanisms that Kurarinol can clear or inhibit HBV of patients with CHB.

Adult ; Drug Administration Schedule ; Female ; Flavonoids ; administration & dosage ; Hepatitis B, Chronic ; drug therapy ; immunology ; Humans ; Immunity, Innate ; drug effects ; Male ; Middle Aged ; Silymarin ; administration & dosage ; T-Lymphocytes, Cytotoxic ; drug effects ; Young Adult

Reactive oxygen species (ROS) production is one of the main mechanisms used to kill microbes during innate immune response. D-lactic acid, which is augmented during acute ruminal acidosis, reduces platelet activating factor (PAF)-induced ROS production and L-selectin shedding in bovine neutrophils in vitro. This study was conducted to investigate whether acute ruminal acidosis induced by acute oligofructose overload in heifers interferes with ROS production and L-selectin shedding in blood neutrophils. Blood neutrophils and plasma were obtained by jugular venipuncture, while ruminal samples were collected using rumenocentesis. Lactic acid from plasma and ruminal samples was measured by HPLC. PAF-induced ROS production and L-selectin shedding were measured in vitro in bovine neutrophils by a luminol chemiluminescence assay and flow cytometry, respectively. A significant increase in ruminal and plasma lactic acid was recorded in these animals. Specifically, a decrease in PAF-induced ROS production was observed 8 h after oligofructose overload, and this was sustained until 48 h post oligofructose overload. A reduction in PAF-induced L-selectin shedding was observed at 16 h and 32 h post oligofructose overload. Overall, the results indicated that neutrophil PAF responses were altered in heifers with ruminal acidosis, suggesting a potential dysfunction of the innate immune response.
Acidosis/chemically induced/immunology/*veterinary ; Animals ; Blood ; Cattle ; Cattle Diseases/chemically induced/*immunology ; Female ; Flow Cytometry/veterinary ; *Immunity, Innate ; L-Selectin/metabolism ; Neutrophils/*drug effects ; Oligosaccharides/*pharmacology/toxicity ; Platelet Activating Factor/*pharmacology ; Reactive Oxygen Species/metabolism ; Rumen

Herbal extracts have been extensively used worldwide for their application on memory improvement, especially among aged and memory-deficit populations. In the present study, the memory loss induced by human Abeta protein over-expression in fruitfly Alzheimer's disease (AD) model was rescued by multiple extracts from Gardenia jasminoides. Three extracts that rich with gardenia yellow, geniposide, and gardenoside components showed distinct rescue effect on memory loss. Further investigation on adding gardenoside into a formula of Ganoderma lucidum, Panax notoginseng and Panax ginseng (GPP) also support its therapeutic effects on memory improvement. Interestingly, the application of GPP and gardenoside did not alter the accumulation of Abeta proteins but suppressed the expression of immune-related genes in the brain. These results revealed the importance and relevancy of anti-inflammation process and the underlying mechanisms on rescuing memory deficits, suggesting the potential therapeutic use of the improved GPP formulation in improving cognition in defined population in the future.
Alzheimer Disease ; drug therapy ; Animals ; Antimicrobial Cationic Peptides ; genetics ; Brain ; drug effects ; immunology ; Cognition ; drug effects ; Disease Models, Animal ; Drosophila ; Drosophila Proteins ; genetics ; Gardenia ; chemistry ; Gene Expression Regulation ; drug effects ; Immunity, Innate ; drug effects ; Iridoids ; chemistry ; isolation & purification ; pharmacology ; Plant Extracts ; chemistry ; isolation & purification ; pharmacology ; Polymerase Chain Reaction