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Sukriti Sukriti Nirupma Trehanpati Manoj Kumar Chandana Pande Syed S. Hissar Shiv Kumar Sarin 《Hepatology International》2016,10(6):916-923
Background
Dendritic cells (DCs) promote pathogen recognition, uptake and presentation of antigen through DC-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) and toll-like receptors (TLRs).Aims and Objectives
We aimed to study temporal changes in DCs, TLRs and DC-SIGN during acute viral hepatitis B (AVHB) infection and compare them to chronic (CHB) and to investigate the earliest time point of activated pathogen recognition receptors in hepatitis B viral infection.Methods
We measured the frequencies of circulating myeloid (mDC) and plasmacytoid (pDC) dendritic cells and IFN-α production along with the expression of DC-SIGN and Toll Like Receptors (TLR's) in HBV patients at different time points. Also investigated in healthy volunteers, the dynamic changes in TLRs expression after receiving hepatitis B vaccine.Results
On follow-up of AVHB patients, we found the mDC population was significantly higher at week 4 and 6 (p < 0.02, 0.01), whereas the pDC population was unchanged at week 6 compared with week 0. Whereas frequencies of mDCs and pDCs were found to be elevated in AVHB and CHB patients than HC (p < 0.00 and 0.01, respectively) but was comparable among AVHB vs CHB. The DCs in CHB patients were functionally impaired with significantly low IFN-α production and low DCSIGN expression (p < 0.04 and 0.00, respectively). Even after stimulation by TLR agonists, no change was found in IFN-α production in CHB patients. MyD88 and IL-6, IFN-α mRNA levels were also found down-regulated. Interestingly, on follow-up after HBV vaccine, TLRs expression was found high at day 3 after vaccination.Discussion
The initial events of immune activation might be responsible for modulating immune response. These novel observations would pave the way for the development of antiviral strategies for chronic HBV infection.2.
Gupta Manisha Krishan Pawan Kaur Amarjot Arora Sandeep Trehanpati Nirupma Singh Thakur Gurjeet Bedi Onkar 《Inflammation research》2021,70(7):765-776
Inflammation Research - Non-alcoholic fatty liver disease (NAFLD) is a multifaceted disease allied with various metabolic disorders, obesity and dysbiosis. Gut microbiota plays an influential role... 相似文献
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TrehanPati N Kotillil S Hissar SS Shrivastava S Khanam A Sukriti S Mishra SK Sarin SK 《Journal of clinical immunology》2011,31(3):509-520
Limited response to current hepatitis B virus (HBV) drugs is possibly due to inadequate host cytotoxic cellular responses.
Circulating Tregs have been shown to be associated with chronicity of HBV infection, but their profile during antiviral therapy
has not been studied. We analyzed the frequency and effect of Tregs on cellular immune responses against HBV in 35 chronic
hepatitis B eAg−ve and eAg+ve patients treated with tenofovir 300 mg/day. Frequency of Tregs and their modulatory role in
cytokine-secreting cells were determined after stimulation with HBsAg or HBcAg in the absence or presence of Tregs and after
blockage of PD-1/PDL-1 in peripheral blood mononuclear cells (PBMCs). Prior to therapy, eAg−ve patients had lower HBV DNA
levels, reduced CD8 T cells, increased Tregs, and T cells expressing PD1. After 12 weeks of therapy, >2 log HBV viral reduction
was observed in both groups, along with an increase frequencies of CD8 T cells in eAg−ve patients and increased expression
of chemokine receptors/Toll-like receptors in both groups. PD-1 expression on CD8 cells in PBMCs was decreased in both groups
during therapy but not on Tregs. In eAg–ve group, sustained increase of Tregs was observed till week 12, which declined at
week 24. In both groups, after 24 weeks, depletion of CD4+CD25+ Tregs from PBMCs enhanced HBV-specific T cell responses, and blockage of PD-1/PDL1 pathway did enhance pro-inflammatory cytokine
production in eAg+ve patients but not in eAg−ve. We conclude that Tregs induced by HBV replication in vivo are expanded in
eAg−ve patients more. Reduction in HBV DNA by tenofovir partially restored adaptive immune responses and also reduced the
Tregs. Blockage of PD-1/PDL1, enhanced cytokine production in eAg+ve patients but not in eAg−ve, suggests that distinctly
different immunologic mechanisms are involved in eAg+ve and eAg−ve patients. 相似文献
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TrehanPati N Sukriti S Geffers R Hissar S Riese P Toepfer T Guzman CA Sarin SK 《Journal of clinical immunology》2011,31(3):498-508
Background and Aims
Approximately 50% of acute viral hepatitis in young adults and in pregnant women is due to hepatitis E virus (HEV) infection in developing countries. T cell-mediated immune injury probably plays a key role in the pathogenesis of acute hepatitis illness. However, there is a paucity of data on the global gene expression programs activated on T cells, which are subsequently responsible for T cell recruitment to the liver and triggering of immune injury. 相似文献7.
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Sukriti Sukriti Nirupma Trehan Pati Sujoy Bose Syed S. Hissar Shiv Kumar Sarin 《Journal of clinical immunology》2010,30(3):419-425