A STAT3-STING-IFN axis controls the metastatic spread of small cell lung cancer.

Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor characterized by a high metastatic potential with an overall survival rate of ~5%. The transcription factor signal transducer and activator of transcription 3 (STAT3) is overexpressed by >50% of tumors, including SCLC, but its role in SCLC development and metastasis is unclear. Here, we show that, while STAT3 deletion restricts primary tumor growth, it paradoxically enhances metastatic spread by promoting immune evasion.

Expression of Interferon Epsilon in Mucosal Epithelium is Regulated by Elf3.

Interferon epsilon (IFNε) is a unique type I interferon (IFN) that shows distinct constitutive expression in reproductive tract epithelium. Understanding how IFNε expression is regulated is critical for the mechanism of action in protecting the mucosa from infection. Combined computational and experimental investigation of the promoter of IFNε predicted transcription factor binding sites for the ETS family of transcription factors.

Epithelially Restricted Interferon Epsilon Protects Against Colitis.

Background & Aims: Type I interferon (T1IFN) signalling is crucial for maintaining intestinal homeostasis. We previously found that the novel T1IFN, IFNε, is highly expressed by epithelial cells of the female reproductive tract, where it protects against pathogens. Its function has not been studied in the intestine.

Distribution patterns of mucosally applied particles and characterization of the antigen presenting cells.

Mucosal application is the most common route of vaccination to prevent outbreaks of infectious diseases like Newcastle disease virus (NDV). To gain more knowledge about distribution and uptake of a vaccine after mucosal vaccination, we studied the distribution pattern of antigens after different mucosal routes of administration. Chickens were intranasally (i.

Differential lung NK cell responses in avian influenza virus infected chickens correlate with pathogenicity.

Infection of chickens with low pathogenicity avian influenza (LPAI) virus results in mild clinical signs while infection with highly pathogenic avian influenza (HPAI) viruses causes death of the birds within 36-48 hours. Since natural killer (NK) cells have been shown to play an important role in influenza-specific immunity, we hypothesise that NK cells are involved in this difference in pathogenicity. To investigate this, the role of chicken NK-cells in LPAI virus infection was studied.

Glycans from avian influenza virus are recognized by chicken dendritic cells and are targets for the humoral immune response in chicken.

To increase our understanding of the interaction between avian influenza virus and its chicken host, we identified receptors for putative avian influenza virus (AIV) glycan determinants on chicken dendritic cells. Chicken dendritic cells (DCs) were found to recognize glycan determinants containing terminal αGalNAc, Galα1-3Gal, GlcNAcβ1-4GlcNAcβ1-4GlcNAcβ (chitotriose) and Galα1-2Gal. Infection of chicken dendritic cells with either low pathogenic (LP) or highly pathogenic (HP) AIV results in elevated mRNA expression of homologs of the mouse C-type lectins DEC205 and macrophage mannose receptor (MMR), whereas expression levels of the human dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) homolog remained unchanged.

Regulation of macrophage and dendritic cell function by pathogens and through immunomodulation in the avian mucosa.

Macrophages (MPh) and dendritic cells (DC) are members of the mononuclear phagocyte system. In chickens, markers to distinguish MPh from DC are lacking, but whether MPh and DC can be distinguished in humans and mice is under debate, despite the availability of numerous markers. Mucosal MPh and DC are strategically located to ingest foreign antigens, suggesting they can rapidly respond to invading pathogens.

Systemic distribution of different low pathogenic avian influenza (LPAI) viruses in chicken.

Background: Since we were able to isolate viable virus from brain and lung of H7N1 low pathogenic avian influenza virus (LPAIV) infected chickens, we here examined the distribution of different LPAIV strains in chickens by measuring the viral AI RNA load in multiple organs. Subtypes of H5 (H5N1, H5N2), H7 (H7N1, H7N7) and H9 (H9N2), of chicken (H5N2, H7N1, H7N7, H9N2), or mallard (H5N1) origin were tested. The actual presence of viable virus was evaluated with virus isolation in organs of H7N7 inoculated chickens.

Induction of respiratory immune responses in the chicken; implications for development of mucosal avian influenza virus vaccines.

The risk and the size of an outbreak of avian influenza virus (AIV) could be restricted by vaccination of poultry. A vaccine used for rapid intervention during an AIV outbreak should be safe, highly effective after a single administration and suitable for mass application. In the case of AIV, aerosol vaccination using live virus is not desirable because of its zoonotic potential and because of the risk for virus reassortment.

Uptake of particulate antigens in a nonmammalian lung: phenotypic and functional characterization of avian respiratory phagocytes using bacterial or viral antigens.

Major distinctive features of avian lungs are the absence of draining lymph nodes and alveoli and alveolar macrophages (MPhs). However, a large network of MPhs and dendritic cells (DCs) is present in the mucosa of the larger airways and in the linings of the parabronchi. For the modulation of respiratory tract immune responses, for example, by vaccination, a better understanding of Ag uptake in the chicken respiratory tract is needed.

A lack of antibody formation against inactivated influenza virus after aerosol vaccination in presence or absence of adjuvantia.

In the poultry industry, infections with avian influenza virus (AIV) can result in significant economic losses. The risk and the size of an outbreak might be restricted by vaccination of poultry. A vaccine that would be used for rapid intervention during an outbreak should be safe to use, highly effective after a single administration and be suitable for mass application.

Kinetics of the avian influenza-specific humoral responses in lung are indicative of local antibody production.

The role and kinetics of respiratory immunoglobulins in AIV infection has not been investigated. In this study we determined the numbers of both total antibody secreting cells (ASC) and virus-specific ASC in lung, spleen, blood and bone marrow (BM) following low-pathogenic AIV infection. Antiviral humoral immune responses were induced both locally in the lung and systemically in the spleen.

Differential expression of adenosine A3 receptors controls adenosine A2A receptor-mediated inhibition of TLR responses in microglia.

Microglia activation is a prominent feature in many neuroinflammatory disorders. Unrestrained activation can generate a chronic inflammatory environment that might lead to neurodegeneration and autoimmunity. Extracellular adenosine modulates cellular activation through adenosine receptor (ADORA)-mediated signaling.

Immunization with mannosylated peptide induces poor T cell effector functions despite enhanced antigen presentation.

In this study, we investigated the development of T cell responses in mice after administration of a mannosylated ovalbumin peptide (M-OVA(323-339)). Immunization with M-OVA(323-339) in complete adjuvant resulted in enhanced antigen presentation in draining lymph nodes. Monitoring the fate of CFSE-labeled ovalbumin peptide-specific TCR transgenic CD4(+) T cells revealed that immunization with M-OVA(323-339) induced normal clonal expansion, recirculation and CD62L expression of antigen-specific T cells in vivo.