Microbiome modifications by steroids during viral exacerbation of asthma and in healthy mice.

In the present studies, the assessment of how viral exacerbation of asthmatic responses with and without pulmonary steroid treatment alters the microbiome in conjunction with immune responses presents striking data. The overall findings identify that although steroid treatment of allergic animals diminished the severity of the respiratory syncytial virus (RSV)-induced exacerbation of airway function and mucus hypersecretion, there were local increases in IL-17 expression. Analysis of the lung and gut microbiome suggested that there are differences in RSV exacerbation that are further altered by fluticasone (FLUT) treatment.

Respiratory Virus-Induced PARP1 Alters DC Metabolism and Antiviral Immunity Inducing Pulmonary Immunopathology.

Previous studies from our laboratory and others have established the dendritic cell (DC) as a key target of RSV that drives infection-induced pathology. Analysis of RSV-induced transcriptomic changes in RSV-infected DC revealed metabolic gene signatures suggestive of altered cellular metabolism. Reverse phase protein array (RPPA) data showed significantly increased PARP1 phosphorylation in RSV-infected DC.

Mucosal IgA immune complex induces immunomodulatory responses in allergic airway and intestinal T2 disease.

Background: IgA is the most abundant immunoglobulin at the mucosal surface and although its role in regulating mucosal immunity is not fully understood, its presence is associated with protection from developing allergic disease.

Objective: We sought to determine the role of IgA immune complexes for therapeutic application to mucosal allergic responses.

Methods: Trinitrophenol (TNP)-specific IgA immune complexes were applied, using TNP-coupled ovalbumin (OVA), to airway and gut mucosal surfaces in systemically sensitized allergic animals to regulate allergen challenge responses.

Role of ILC2 in Viral-Induced Lung Pathogenesis.

Innate lymphoid type-2 cells (ILC2) are a population of innate cells of lymphoid origin that are known to drive strong Type 2 immunity. ILC2 play a key role in lung homeostasis, repair/remodeling of lung structures following injury, and initiation of inflammation as well as more complex roles during the immune response, including the transition from innate to adaptive immunity. Remarkably, dysregulation of this single population has been linked with chronic lung pathologies, including asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrotic diseases (IPF).

ER stress protein PERK promotes inappropriate innate immune responses and pathogenesis during RSV infection.

The activation of dendritic cells (DC) during respiratory viral infections is central to directing the immune response and the pathologic outcome. In these studies, the effect of RSV infection on development of ER stress responses and the impact on innate immunity was examined. The upregulation of ER stress was closely associated with the PERK pathway through the upregulation of CHOP in RSV infected DC.

Role of Mitochondria in Viral Infections.

Viral diseases account for an increasing proportion of deaths worldwide. Viruses maneuver host cell machinery in an attempt to subvert the intracellular environment favorable for their replication. The mitochondrial network is highly susceptible to physiological and environmental insults, including viral infections.

Sirtuin 1 regulates mitochondrial function and immune homeostasis in respiratory syncytial virus infected dendritic cells.

Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infection in children worldwide. Sirtuin 1 (SIRT1), a NAD+ dependent deacetylase, has been associated with induction of autophagy, reprogramming cellular metabolism, and regulating immune mediators. In this study, we investigated the role of SIRT1 in bone marrow dendritic cell (BMDC) function during RSV infection.

Alpha-D-glucan nanoparticulate adjuvant induces a transient inflammatory response at the injection site and targets antigen to migratory dendritic cells.

Biodegradable nanoparticles with functionalized surfaces are attractive candidates as vaccine adjuvants. Nano-11 are cationic dendrimer-like -D-glucan nanoparticles with a diameter of 70-80 nm. Mice injected with antigen formulated with Nano-11 developed antibody titers that were similar or greater than antigen with aluminum adjuvant.

Transcription factor Foxo1 is essential for IL-9 induction in T helper cells.

Interleukin 9 (IL-9)-producing helper T (Th9) cells have a crucial function in allergic inflammation, autoimmunity, immunity to extracellular pathogens and anti-tumor immune responses. In addition to Th9, Th2, Th17 and Foxp3 regulatory T (Treg) cells produce IL-9. A transcription factor that is critical for IL-9 induction in Th2, Th9 and Th17 cells has not been identified.

Identification of GR and TrxR systems in Setaria cervi: Purification and characterization of glutathione reductase.

The glutathione reductase (GR) and thioredoxin reductase (TrxR) are important enzymes of the redox system that aid parasites to maintain an adequate intracellular redox environment. In the present study, the enzyme activity of GR and TrxR was investigated in Setaria cervi (S. cervi).

Identification of Setaria cervi heat shock protein 70 by mass spectrometry and its evaluation as diagnostic marker for lymphatic filariasis.

Using mass spectrometry and immunological approaches, a heat shock protein 70 associated with lymphatic filariasis (LF) has been identified from a bovine filarial parasite Setaria cervi. A heat shock protein was detected in different life stages of S. cervi when exposed to an elevated temperature of 44 degrees C.

Screening of different classes of proteases in microfilarial and adult stages of Setaria cervi.

Many of the filarial proteases involved in critical physiological functions are expressed in stage-specific manner and belong to various mechanistic classes. Setaria cervi, a bovine filarial parasite express different classes of proteases. This parasite shows strong antigenic cross-reactivity with human filarial parasites Wuchereria bancrofti and Brugia malayi.