Changes in cellular proliferation and plasma products are associated with liver failure

AIM To study the differences in immune response and cytokine profile between acute liver failure and selflimited acute hepatitis.METHODS Forty-six patients with self-limited acute hepatitis(AH), sixteen patients with acute liver failure(ALF), and twenty-two healthy subjects were involved in this study. The inflammatory and anti-inflammatory products in plasma samples were quantified using commercial enzyme-linked immunoassays and quantitative real-time PCR. The cellular immune responses were measured by proliferation assay using flow cytometry. The groups were divided into viral- and non-viral-induced selflimited AH and ALF. Thus, we worked with five groups: Hepatitis A virus(HAV)-induced self-limited acute hepatitis(HAV-AH), HAV-induced ALF(HAV-ALF), nonviral-induced self-limited acute hepatitis(non-viral AH), non-viral-induced acute liver failure(non-viral ALF), and healthy subjects(HC). Comparisons among HAV and non-viral-induced AH and ALF were performed.RESULTS The levels of mitochondrial DNA(mt DNA) and the cytokines investigated [interleukin(IL)-6, IL-8, IL-10, interferon gamma, and tumor necrosis factor] were significantly increased in ALF patients, independently of etiology(P < 0.05). High plasma mt DNA and IL-10 were the best markers associated with ALF [mt DNA: OR = 320.5(95%CI: 14.42-7123.33), P < 0.0001; and IL-10: OR = 18.8(95%CI: 1.38-257.94), P = 0.028] and death [mt DNA: OR = 12.1(95%CI: 2.57-57.07), P = 0.002; and IL-10: OR = 8.01(95%CI: 1.26-50.97), P = 0.027]. In the cellular proliferation assay, NK^(bright), NKT and regulatory T cells(TReg) predominated in virusspecific stimulation in HAV-induced ALF patients with an anergic behavior in the cellular response to mitotic stimulation. Therefore, in non-viral-induced ALF, anergic behavior of activated T cells was not observed after mitotic stimulation, as expected and as described by the literature. CONCLUSION mt DNA and IL-10 may be predictors of ALF and death. TReg cells are involved in immunological disturbance in HAV-induced ALF.

Chimeric flagellin expressed by Salmonella typhimurium induces an ESAT-6-specific Th1-type immune response and CTL effects following intranasal immunization

The flagellin component FliC of Salmonella typhimurium is capable of activating the innate immune system via specific interactions with TLR5 and can also act as a carrier of foreign antigen to elicit antigen-specific immune responses.Thus,we constructed an attenuated Salmonella strain SL5928(fliC/esat)expressing chimeric flagellin that contained the ESAT-6 antigen coding sequence of Mycobacterium tuberculosis inserted into the highly variable region of the Salmonella flagellin coding gene fliCi.The chimeric flagellin functioned normally,as demonstrated using a flagella swarming assay and electron microscopy.To analyze the effects of chimeric flagellin,the cell-mediated immune response and cytotoxic T lymphocyte(CTL)effects specific for ESAT-6 antigen were tested after intranasal immunization of mice with flagellated Salmonella SL5928(fliC/esat).The results showed that SL5928(fliC/esat)intranasal immunization can strongly elicit an ESAT-6-specific T helper(Th)1-type immune response in mucosal lymphoid tissues,such as nasopharynx-associated lymph nodes,lung and Peyer’s patches,and a Th1/Th2 response was elicited in spleen and mesenteric lymph nodes.Furthermore,intranasal immunization of SL5928(fliC/esat)produced efficient CTL effects,as demonstrated using a 5-and 6-carboxyfluorescein diacetate succinimidyl ester(CFSE)assay.Thus,our study revealed that Salmonella flagellin acts as a carrier for foreign antigen and triggers strong Th1 and CTL responses during intranasal immunization.Chimeric flagellin is potentially an effective strategy for the development of novel vaccines against tuberculosis in humans and animals.

Rho 1 participates in parasitoid wasp eggs maturation and host cellular immunity inhibition

Endoparasitoid wasps introduce venom into their host insects during the egglaying stage.Venom proteins play various roles in the host physiology,development,immunity,and behavior manipulation and regulation.In this study,we identified a venom protein,MmRhol,a small guanine nucleotide-binding protein derived from ovary in the endoparasitoid wasp Microplitis mediator and found that knockdown of its expression by RNA interference caused down-regulation of vitellogenin and juvenile hormone,egg production,and cocoons formation in the female wasps.We demonstrated that MmRho1 entered the cotton bollworm's(host)hemocytes and suppressed cellular immune responses after parasitism using immunofluorescence staining.Furthermore,wasp MmRhol interacted with the cotton bollworm's actin cytoskeleton rearrangement regulator diaphanous by yeast 2-hybrid and glutathione s-transferase pull-down.In conclusion,this study indicates that MmRho1 plays dual roles in wasp development and the suppression of the host insect cellular immune responses.

A DNA-Binding Bromodomain-Containing Protein Interacts with and Reduces Rx1-Mediated Immune Response to Potato Virus X

Plant NLR proteins enable the immune systemto recognize and respond to pathogen attack.An early consequence of immune activation is transcriptional reprogramming.SomeNLRs have been shownto act in the nucleus and interact with transcription factors.The Rx1 NLR protein of potato binds and distorts doublestranded DNA.However,the components of the chromatin-localized Rx1 complex are largely unknown.Here,we report a physical and functional interaction between Rx1 and NbDBCP,a bromodomaincontaining chromatin-interacting protein.NbDBCP accumulates in the nucleoplasmand nucleolus,interacts with chromatin,and redistributes Rx1 tothe nucleolus in a subpopulation of imaged cells.Rx1 overexpression reduces the interaction between NbDBCP and chromatin.NbDBCP is a negative regulator of Rx1-mediated immune responses to potato virus X(PVX),and this activity requires an intact bromodomain.Previously,Rx1 has been shown to regulate the DNA-binding activity of a Golden2-like transcription factor,NbGlk1.Rx1 and NbDBCP act synergistically to reduce NbGlk1 DNA binding,suggesting a mode of action for NbDBCP’s inhibitory effect on immunity.This study provides new mechanistic insight into the mechanism by which a chromatin-localized NLR complex co-ordinates immune signaling after pathogen perception.