Effectiveness of Andrographis paniculata Extract Nanoparticle on The Expression of CD4+ and CD8+ of Rats Listeriosis

The unrelenting bombardment by microbial pathogens from the environment and their increasing resistance to medical treatments are a constant threat to the survival of all organisms on earth. Microbes are covered by molecular patterns that are common among a broad range of pathogens. These include the lipopolysaccharides (LPS) of Gram-negative bacteria, lipoteichoic acids of Gram-positive bacteria, lipoproteins of bacteria and parasites, glycolipids of mycobacteria, mannans of yeast and double-stranded RNAs of viruses.1,2 Recognition of and responses to these molecules are controlled by a wide variety of cellular receptors. The best characterized receptors are the T-cell receptor and B-cell antibody receptor of the adaptive immune response, the specificity of which is randomly generated and clonally selected during the development of T and B lymphocytes.3 Unlike the receptors of the adaptive immune system, the pattern recognition receptors of the innate immune system have predetermined specificity generated early on in evolution and play an essential role in the determination of self versus non-self during the initial rapid responses to infection.1,2 As described in this review, a family of cell surface receptors, termed Toll-like receptors, are emerging as key regulators of host responses to infection.

IL-21 Enhances Antitumor Responses without Stimulating Proliferation of Malignant T Cells of Patients with Sézary Syndrome

Emerging role of neuregulin-1beta1 in pathogenesis and progression of multiple sclerosis

Transient Pretreatment With Glucocorticoid Ablates Innate Toxicity of Systemically Delivered Adenoviral Vectors Without Reducing Efficacy

Phagosomes are critical compartments for innate immunity. However, their role in the protection against murine listeriosis has not been examined. We describe here that listericidal phago-receptosomes are induced by the function of IFN-γ or IL-6 as centralized compartments for innate and adaptive immunity because they are able to confer protection against murine listeriosis. These phago-receptosomes elicited LLO(91-99)/CD8(+)- and LLO(189-201)/CD4(+)-specific immune responses and recruited mature dendritic cells to the vaccination sites controlled by T cells. Moreover, they present exceptional features as efficient vaccine vectors. First, they compartmentalize a novel listericidal STAT-1-mediated signaling pathway that confines multiple innate immune components to the same environment. Second, they show features of MHC class II antigen-loading competent compartments for cathepsin-D-mediated LLO processing. Third, murine cathepsin-D deficiencies fail to develop protective immunity after vaccination with listericidal phago-receptosomes induced by IFN-γ or IL-6. Therefore, it appears that the connection of STAT-1 and cathepsin-D in a single compartment is relevant for protection against listeriosis.

Innate and adaptive immune responses to Listeria monocytogenes: a short overview

Rip2: a novel therapeutic target for bacteria-induced inflammation?

Porcine reproductive and respiratory syndrome (PRRS) is a devastating viral disease affecting swine production, health and welfare throughout the world. Vaccination has been considered as one of the most economic tools for PRRS control. A synergistic action of the innate and the adaptive immune system of host is essential for developing a durable protective immunity to vaccine antigen. The peripheral blood mononuclear cells (PBMCs) play central role in immune system and are able to display gene expression patterns characteristics for certain infection. Therefore, the current study aimed to investigate the global transcriptome profiles of PBMCs to characterize the innate and the adaptive immune response to PRRS Virus (PRRSV) vaccine in Pietrain pigs. We employed nine Affymetrix gene chip porcine gene 1.0 ST array for the transcriptome profiling of PBMCs collected from three female piglets at immediately before (D0), at one (D1) and 28 d (D28) post PRRSV vaccination given at 4 wk (D0) of their age. Two pairwise contrasts were tested to characterize transcriptome alterations associated with the innate immune response (D1 vs. D0) and the adaptive immune response (D28 vs. D0). Normalization and statistical analysis of microarray data was performed with the ‘oligo’ and ‘limma’ R/Bioconductor package. With FDR < 0.05 and log2 fold change ± 1.5 as cutoff criteria, 83 and 53 transcripts were found to be differentially expressed in PBMCs during innate and adaptive response, respectively. The microarray expression results were technically validated by qRT-PCR. The gene ontology (GO) terms such as viral life cycle, regulation of lymphocyte activation, cytokine activity and inflammatory response were enriched during the innate immune response. The GO terms enriched during adaptive response includes cytolysis, T cell mediated cytotoxicity, immunoglobulin production. Significant enrichment of cytokine-cytokine receptor interaction, signaling by interleukins, viral mRNA translation, IFN-γ pathway and AP-1 transcription factor network pathways was indicating the involvement of altered genes in the antiviral defense. Network analysis has detected four module were functionally involved with functional network of innate immune transcriptional response and five modules were detected for adaptive immune responses. The innate immune transcriptional network found to be regulated by LCK, STAT3, ATP5B, UBB and RSP17. While TGFβ, IL7R, RAD21, SP1 and GZMB are responsible for coordinating the adaptive immune transcriptional response to PRRSV vaccine in PBMCs. Further work is required to determine whether polymorphisms linked to these genes affect the immune response to PRRSV vaccine in pigs.

Targeting Innate Immunity: A New Step in the Development of Combination Therapy for Chronic Hepatitis B

BackgroundCD1d is a nonpolymorphic MHC class I-like molecule which presents nonpeptide ligands, e.g. glycolipids, to NKT cells. These cells are known to have multiple effects on innate and adaptive immune responses and on the development of pathological conditions. In order to analyze CD1d expression and function in the rat, the first rat CD1d-specific monoclonal antibodies (mAbs) were generated.Methodology/Principal FindingsTwo mAbs, WTH-1 and WTH-2, were generated which bound equally well to cell surface-expressed rat and mouse CD1d. Their non-overlapping epitopes were mapped to the CD1d heavy chain. Flow cytometry and immunohistological analyses revealed a nearly identical degree and pattern of CD1d expression for hematopoieitic cells of both species. Notable is also the detection of CD1d protein in mouse and rat Paneth cells as well as the extremely high CD1d expression in acinar exocrine cells of the rat pancreas and the expression of CD4 on rat marginal zone B cells. Both mAbs blocked α-galactosylceramide recognition by primary rat and mouse NKT cells. Interestingly, the two mAbs differed in their impact on the activation of various autoreactive T cell hybridomas, including the XV19.2 hybridoma whose activation was enhanced by the WTH-1 mAb.Conclusions/SignificanceThe two novel monoclonal antibodies described in this study, allowed the analysis of CD1d expression and CD1d-restricted T cell responses in the rat for the first time. Moreover, they provided new insights into mechanisms of CD1d-restricted antigen recognition. While CD1d expression by hematopoietic cells of mice and rats was extremely similar, CD1d protein was detected at not yet described sites of non-lymphatic tissues such as the rat exocrine pancreas and Paneth cells. The latter is of special relevance given the recently reported defects of Paneth cells in CD1d−/− mice, which resulted in an altered composition of the gut flora.

A Role for Human SPα as a Pattern Recognition Receptor

Toll-like Receptor 9 Triggers an Innate Immune Response to Helper-dependent Adenoviral Vectors

Aprominent pathology textbook used in the United States includes an image illustrating the renal histopathology caused by malignant hypertension. The legend describes striking “onion skin” changes of a renal arteriole. Curiously, a sea of mononuclear inflammatory cells surrounding this arteriole is overlooked both in the legend and in the related text. Moreover, nothing regarding inflammation or immune reactions is discussed. This lack of attention to inflammatory cells is, however, not surprising. Although many experimental studies have implicated inflammation in hypertension, these have largely been performed in experimental animals; there is no proof that inflammation contributes to human hypertension. In fact, some anti-inflammatory or immune-suppressing drugs (eg, nonsteroidal anti-inflammatory drugs and cyclosporine) paradoxically cause hypertension in humans, likely via off-target effects. Often the term “inflammation” is used in the context of cardiovascular disease as a catchall referring to nonspecific phenomena, such as elevation of C-reactive protein or the presence of macrophages in a tissue. Most clinicians and investigators find this vague and difficult to understand. Even more puzzling is that many studies now implicate the adaptive immune response, and in particular, lymphocytes, in hypertension and vascular disease. Traditionally, bacterial, viral, or tumor antigens activate this arm of immune defense. As such, it has been hard to imagine how adaptive immunity could be involved in a disease such as hypertension. In this article, we will attempt to address some of these puzzling questions. We will briefly review components of the innate and adaptive immune response, discuss data from many groups, including our own, that suggest that common forms of hypertension are immune mediated, and provide a working hypothesis of how signals from the central nervous system trigger an immune response that causes hypertension. ### General Concepts Regarding Inflammation and Immunity #### Innate Immunity The first line of defense against pathogens is the innate immune response. Important components of this system include epithelial …

Listeria monocytogenes (LM) is a gram-positive bacterium that is a common contaminant of processed meats and dairy products. In humans, ingestion of LM can result in intracellular infection of the spleen and liver, which can ultimately lead to septicemia, meningitis, and spontaneous abortion. Interleukin (IL)-23 is a cytokine that regulates innate and adaptive immune responses by inducing the production of IL-17A, IL-17F, and IL-22. We have recently demonstrated that the IL-23/IL-17 axis is required for optimal recruitment of neutrophils to the liver, but not the spleen, during LM infection. Furthermore, these cytokines are required for the clearance of LM during systemic infection. In other infectious models, IL-22 induces the secretion of anti-microbial peptides and protects tissues from damage by preventing apoptosis. However, the role of IL-22 has not been thoroughly investigated during LM infection. In the present study, we show that LM induces the production of IL-22 in vivo. Interestingly, IL-23 is required for the production of IL-22 during primary, but not secondary, LM infection. Our findings suggest that IL-22 is not required for clearance of LM during primary or secondary infection, using both systemic and mucosal models of infection. IL-22 is also not required for the protection of LM infected spleens and livers from organ damage. Collectively, these data indicate that IL-22 produced during LM infection must play a role other than clearance of LM or protection of tissues from pathogen- or immune-mediated damage.

Age-related changes in immune function: Effect on airway inflammation