HVEM is a TNF Receptor with Multiple Regulatory Roles in the Mucosal Immune System

The herpes virus entry mediator (HVEM) is a member of the tumor necrosis factor receptor superfamily (TNFRSF), and therefore it is also known as TNFRSF14 or CD270 (1,2). In recent years, we have focused on understanding HVEM function in the mucosa of the intestine, particularly on the role of HVEM in colitis pathogenesis, host defense and regulation of the microbiota (2,3,4). HVEM is an unusual TNF receptor because of its high expression levels in the gut epithelium, its capacity to bind ligands that are not members of the TNF super family, including immunoglobulin (Ig) superfamily members BTLA and CD160, and its bi-directional functionality, acting as a signaling receptor or as a ligand for the receptor BTLA. Clinically, Hvem recently was reported as an inflammatory bowel disease (IBD) risk gene as a result of genome wide association studies (5,6). This suggests HVEM could have a regulatory role influencing the regulation of epithelial barrier, host defense and the microbiota. Consistent with this, using mouse models, we have revealed how HVEM is involved in colitis pathogenesis, mucosal host defense and epithelial immunity (3,7). Although further studies are needed, our results provide the fundamental basis for understanding why Hvem is an IBD risk gene, and they confirm that HVEM is a mucosal gatekeeper with multiple regulatory functions in the mucosa.

Protective Effect of Ginsan Against Vibrio vulnificus Infection

Ginsan, a botanic polysaccharide extracted from Panax ginseng, has recently been reported to modulate mucosal immune response. In this study, we investigated the protective effect of Ginsan against fatal Vibrio vulnificus mucosal infection. A lethal dose of V. vulnificus (1.0 x 106 CFU/mouse) was nasally inoculated to mice. The bacterial count in the nasal associated lymphoid tissue (NALT) of the mouse was significantly reduced in the Ginsan-treated group. The Ginsan-treated group showed improved survival compared to the control group (100% vs 18%). To elucidate the effect of Ginsan on modulating host immune response, cytokine mRNA expressions involved in mediating inflammation were determined by semiquantitative RT-PCR in the NALTs of the infected mice. Most of the cytokine mRNAs were similarly expressed as the control group. However, COX-1 mRNA expression level was higher in Ginsan-treated group compared to the control group. The protective effect of Ginsan was antagonized by treating with a specific COX-1 inhibitor, SC-560. Thus, these data suggest that the protective effect of Ginsan against V. vulnificus infection is partly mediated by modulating COX-1 expression.

Locally produced mucosal IgG in chickens immunized with conventional vaccines for Newcastle disease virus

Newcastle disease virus (NDV) is the causative agent of an economically important disease, which affects all species of birds worldwide. Current vaccination programs for NDV include the use of either low-virulent live-virus vaccines or inactivated vaccines to induce protective immunity while producing minimal adverse effects in birds. In order to further characterize the immune response elicited by live virus and inactivated NDV conventional vaccines in chickens, we evaluated the presence of specific antibodies in different secretions and in tissue culture supernatants of immunized birds. To this end, we analyzed all the samples by ELISA, using an indirect assay set up in the laboratory. Specific anti-NDV IgG antibodies were detected in tracheal and cloacal swabs and tracheal and intestinal washes of immunized animals. We also found specific anti-NDV IgG antibodies in tracheal and intestinal tissue culture supernatants, indicating that the IgG found in swabs and washes was not transudated from serum or, at least, was not all transudated from serum. Knowledge about the mechanisms involved in the immune response of chickens to different NDV vaccines should increase our understanding of the mucosal response against the virus and, eventually, provide new useful information for the development and evaluation of synthetic vaccines.

Autoimmune syndrome induced by chronic mucosal immune response / 中国免疫学杂志

To explore me chanisms of successful induction of autoimmunity by chronic Campylobacter jejuni (CJ-S131 ) infection [3, 4, 5, 6], a chronic mucosal immune response mooe(?) was established by oral immunization of BALB /C mice with formalized CJ-S131 bacteria.in a dosage of 4 xlO8 bacterial cells per mouse, twice a week for 14 weeks, which mimicked the released antigens persistently stimulating the mucosal immune system when mice were chronically infected by C. jejuni. It was also found that the immunized mice demonstrated (?)upus-like autoimmune syndro me, sim ilar, but more severe.to those seen in the mice chronically infected by C. jejuni. It was characterized by (1) significant lymphoproliferation of both mucosal and systemic immune systems; (2) polyclonal activation of B lymphocytes; (3) significantly elevated level of multiple autoanti bodies against ss- DNA, ds- DNA and histones; (4) immunocom plex glomerulonephritisi; (5) chronic inflammation of multiple organs or tissues including the intestine, liver and blood vessels. In the polyclonal activation testin vitro, the levels of total immunoglobulins and autoantibody against DNA in the supernatan ts of the splenic culture cells from the immunized mice were significantly higher than that from the controll mice. The results verified that chronic C. jejuni infection in the gut could induce abnormal. chronic mucosal immune response which led to perturbation of the systemic immune system, resulting autoimmunity or autoimmune syndrom.