Type I interferons are critical antiviral cytokines produced following herpes simplex virus type-1 (HSV-1) infection that act to inhibit viral spread. In the present study, we identify HSV-infected and adjacent unin...Type I interferons are critical antiviral cytokines produced following herpes simplex virus type-1 (HSV-1) infection that act to inhibit viral spread. In the present study, we identify HSV-infected and adjacent uninfected corneal epithelial cells as the source of interferon-a. We also report mice deficient in the A1 chain of the type I IFN receptor (CDl18-/) are extremely sensitive to ocular infection with low doses (100 PFU) of HSV-1 as seen by significantly elevated viral titers in the cornea Compared to wild type (WT) controls. The enhanced susceptibil- ity correlated with a loss of CD4+ and CD8+ T cell recruitment and aberrant chemokine production in the cornea despite mounting an adaptive immune response in the draining mandibular lymph node of CDll8/ mice. Taken together, these results highlight the importance of IFN production in both the innate immune response as well as eliciting chemokine production required to facilitate adaptive immune cell trafficking.展开更多
This study was aimed to evaluate the long-term effects of telbivudine(Ld T) in the treatment of chronic hepatitis B(CHB) and HBV-related liver cirrhosis(LC) and to observe the changes of immunological responses ...This study was aimed to evaluate the long-term effects of telbivudine(Ld T) in the treatment of chronic hepatitis B(CHB) and HBV-related liver cirrhosis(LC) and to observe the changes of immunological responses during Ld T treatment. Clinical data of 80 CHB and 28 HBV-related LC patients who were administered with Ld T for 108 weeks and followed up were retrospectively analyzed. The liver function indicators including ALT, AST and γ-GT, HBV DNA copy number in serum and the rates of hepatitis B e antigen(HBe Ag) seroconversion were analyzed before and 12, 24, 36, 48, 60, 72, 84, 96 and 108 weeks after Ld T treatment in CHB and LC groups. Four serum fibrosis-related markers, including hyaluronic acid(HA), human laminin(LN), human type Ⅳ collagen(Ⅳ-C) and human N-terminal procollagen Ⅲ peptide(PC-Ⅲ), were detected before and after Ld T treatment in LC group. The results showed favorable viral suppression and biochemical responses after treatment with Ld T for 12 weeks, and a high rate of virological and biochemical control was maintained during the course of 108-week treatment in both CHB and LC groups. The four fibrosis-related markers, especially HA and LN, were down-regulated to some degrees in LC group. Moreover, Ld T treatment led to the fluctuation of the circulating interferon-γ(IFN-γ) and interleukin-10(IL-10) levels at different time points in CHB group. It was concluded that Ld T could favorably lead to the virological suppression and biochemical remission. Besides, IFN-γ and IL-10 may represent a suitable and effective predictor of responsiveness during Ld T therapy.展开更多
基金supported by USPHS grant (No. AI053108) to DanielJ.J. CarrP20 (No. RR017703)+1 种基金an unrestricted grant from Research to Prevent Blindnesssupported by NIAID training grant(No. AI007633)
文摘Type I interferons are critical antiviral cytokines produced following herpes simplex virus type-1 (HSV-1) infection that act to inhibit viral spread. In the present study, we identify HSV-infected and adjacent uninfected corneal epithelial cells as the source of interferon-a. We also report mice deficient in the A1 chain of the type I IFN receptor (CDl18-/) are extremely sensitive to ocular infection with low doses (100 PFU) of HSV-1 as seen by significantly elevated viral titers in the cornea Compared to wild type (WT) controls. The enhanced susceptibil- ity correlated with a loss of CD4+ and CD8+ T cell recruitment and aberrant chemokine production in the cornea despite mounting an adaptive immune response in the draining mandibular lymph node of CDll8/ mice. Taken together, these results highlight the importance of IFN production in both the innate immune response as well as eliciting chemokine production required to facilitate adaptive immune cell trafficking.
文摘This study was aimed to evaluate the long-term effects of telbivudine(Ld T) in the treatment of chronic hepatitis B(CHB) and HBV-related liver cirrhosis(LC) and to observe the changes of immunological responses during Ld T treatment. Clinical data of 80 CHB and 28 HBV-related LC patients who were administered with Ld T for 108 weeks and followed up were retrospectively analyzed. The liver function indicators including ALT, AST and γ-GT, HBV DNA copy number in serum and the rates of hepatitis B e antigen(HBe Ag) seroconversion were analyzed before and 12, 24, 36, 48, 60, 72, 84, 96 and 108 weeks after Ld T treatment in CHB and LC groups. Four serum fibrosis-related markers, including hyaluronic acid(HA), human laminin(LN), human type Ⅳ collagen(Ⅳ-C) and human N-terminal procollagen Ⅲ peptide(PC-Ⅲ), were detected before and after Ld T treatment in LC group. The results showed favorable viral suppression and biochemical responses after treatment with Ld T for 12 weeks, and a high rate of virological and biochemical control was maintained during the course of 108-week treatment in both CHB and LC groups. The four fibrosis-related markers, especially HA and LN, were down-regulated to some degrees in LC group. Moreover, Ld T treatment led to the fluctuation of the circulating interferon-γ(IFN-γ) and interleukin-10(IL-10) levels at different time points in CHB group. It was concluded that Ld T could favorably lead to the virological suppression and biochemical remission. Besides, IFN-γ and IL-10 may represent a suitable and effective predictor of responsiveness during Ld T therapy.