From host to population: Bridging the viral immuno-evolutionary gap.

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

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

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

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.

Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) are the most common cause of genital ulceration in humans worldwide. Typically, HSV-1 and 2 infections via mucosal route result in a lifelong latent infection after peripheral replication in mucosal tissues, thereby providing potential transmission to neighbor hosts in response to reactivation. To break the transmission cycle, immunoprophylactics and therapeutic strategies must be focused on prevention of infection or reduction of infectivity at mucosal sites. Currently, our understanding of the immune responses against mucosal infection of HSV remains intricate and involves a balance between innate signaling pathways and the adaptive immune responses. Numerous studies have demonstrated that HSV mucosal infection induces type I interferons (IFN) via recognition of Toll-like receptors (TLRs) and activates multiple immune cell populations, including NK cells, conventional dendritic cells (DCs), and plasmacytoid DCs. This innate immune response is required not only for the early control of viral replication at mucosal sites, but also for establishing adaptive immune responses against HSV antigens. Although the contribution of humoral immune response is controversial, CD4+ Th1 T cells producing IFN-γ are believed to play an important role in eradicating virus from the hosts. In addition, the recent experimental successes of immunoprophylactic and therapeutic compounds that enhance resistance and/or reduce viral burden at mucosal sites have accumulated. This review focuses on attempts to modulate innate and adaptive immunity against HSV mucosal infection for the development of prophylactic and therapeutic strategies. Notably, cells involved in innate immune regulations appear to shape adaptive immune responses. Thus, we summarized the current evidence of various immune mediators in response to mucosal HSV infection, focusing on the importance of innate immune responses.

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

HIV/host interactions: new lessons from the Red Queen's country.

Gene Therapy Research at the Frontiers of Viral Immunology

Research into the effects of host genetics on HIV disease susceptibility and progression, and on the efficacy and toxicity of drug treatment, occupies a particular position in the landscape of HIV research...

Similar to higher vertebrates, the immune system of fish is composed of two major components, innate (non-specific) and adaptive (specific) immune responses. However, the innate immune system in fish has a fundamental importance in preventing pathogen entry as the adaptive immune responses are less efficient compared to mammals. The components of the innate immune system in fish are commonly divided into three compartments: physical parameters, humoral parameters, and cellular factors. Recently, the fish professional APCs received more attention resulting in the increased numbers of studies on their morphology and function. Following a lengthy gap, in the last decades, considerable progress has been made in the mechanistic understanding of fish APC-dependent immune responses. Dendritic cells (DCs), the universal APCs and the major players in bridging and shaping both innate and adaptive immune responses have been characterized in several teleost fish based on their morphology and function. In addition to innate immunity, macrophages have been demonstrated as essential in initiation of adaptive immunity as another professional APCs in teleost fish. Like in mammals, teleost B cells were characterized as important APCs that activate naïve T cells and initiate adaptive immunity. In this study, we provide an overview of innate immune responses in teleost fish and discuss the current status of the field of teleost fish DCs, macrophages and B cells as professional APCs.

This paper presents a study of the flow of ice in wedge-shaped converging channels. Such flows are encountered in the relatively constricted waters of the Canadian Arctic Archipelago. Ridging, lead opening patterns, development of a highpressure area, and arch formation are some of the processes which take place during ice flow through converging channels. An idealized geometry and steady wind forcing were used in the testing. The results give ice cover velocity, distribution of stresses, ice thickness, area coverage and ridging. Some of the conditions leading to arch formation at the constricted exit of the channel are explored.

Cardiovascular diseases (CVDs) are one of the leading causes of mortality worldwide.1 It has been so for decades, notwithstanding a wide array of – mostly preventive – treatment modalities targeting known risk factors, such as hyperlipidemia, type 2 diabetes mellitus, hypertension, or obesity. Recent technical and conceptual advances have unveiled important contributions of the immune system in the pathophysiology of a variety of CVDs such as atherosclerosis, ischemic stroke, chronic heart failure, and other myocardial conditions like myocardial ischemia and reperfusion, viral myocarditis, and cardiac transplantation.2–4 In many of these disorders, so-called danger-associated molecular patterns (DAMPs), released from necrotic tissue and dying cells, can lead to the activation of certain immune cell populations such as monocytes/ macrophages, granulocytes, and T cells, thus aggravating ongoing inflammatory processes at the lesion site. Dendritic cells (DCs) are key modulators of immunity, pivotal in directing innate and adaptive immune responses against microbial, viral, but also modified self-antigens present at the sites of injury. Given the tissue trauma underlying various CVDs, it is not surprising that recent observations have allocated a regulatory role for DCs in CVD-associated immune responses. Interestingly, nondiseased arteries of young individuals were seen to host a network of resident vascular DCs (CD1a+ S100+ lag+ CD31− CD83− CD86−),5 representing a phenotype related to Langerhans cells in the skin. In agreement, monocyte-derived CD11c+ CD68+ dendritic cells could be detected in the atherosclerosis-prone lesser curvature and aortic sinus in inbred atherosclerosis-susceptible (C57Bl/6), but not resistant mouse strains (balb/c).6 Murine vascular resident DCs express an immature phenotype with low expression of costimulatory molecules, and are present in the subendothelial space with occasional probing into the vascular lumen. DCs have …

Introduction The expression of CD47 on tumor cells can act as a "don't eat me signal" against phagocytosis by macrophages and dendritic cells. Moreover, PD-L1-expressing tumor cells inhibit the anti-tumor activity of cytotoxic T cells. Circulating tumor cells (CTCs) expressing these molecules could overcome elimination by the immune system. In the current study, we evaluated for the first time the co-expression of CD47 and PD-L1 on single CTCs from patients with metastatic breast cancer (mBC). Methods Triple immunofluorescence staining was performed on peripheral blood mononuclear cells (PBMC) cytospin preparations from 18 CTC-positive patients with mBC, using antibodies against cytokeratins (for CTC detection), CD47 and PD-L1. Blood samples were obtained before the initiation of first-line chemotherapy. A total of 1*106 PBMCs were analyzed per patientusing the Ariol microscopy system. The expression levels of CD47 and PD-L1 were characterized as high or low/-, after quantification by the Ariol system, using the MDA.MB.231 breast cancer cell line as positive control. Results A total of 23 CTCs (median: 1, range: 1-4) were identified. CD47-expressing CTCs were detected in 94.4% of patients and represented 91.3% of total CTCs. However, high CD47 expression was confirmed in 38.9% and 43.5% of patients and CTCs, respectively. PD-L1 expression was evident in 27.8% of patients and in 21.7% of CTCs, whereas CTCs expressing high levels of PD-L1 were identified in 16.% of patients and represented 13% of total CTCs. Co-expression of CD47 and PD-L1 (CD47+/PD-L1+) was observed in 21.7% of CTCs, whereas 69.6% of CTCs expressed CD47 only (CD47+/PD-L1-). No CTCs expressing only PD-L1 (CD47-/PD-L1+) were detected and 2 of 23 cells were negative for both markers (CD47-/PD-L1- ). Regarding the differential expression levels of CD47 and PD-L1, the phenotype CD47low/-/PD-L1low/- was the most abundant both at the patient (61.1%) and the CTC level (52.2%). CD47high/PD-L1low/- CTCswere observed in 33.3% and 34.8% of patients and CTCs, respectively whereas only 1 CD47low/-/PD-L1high CTC was detected in one patient. Interestingly, CD47high/PD-L1high CTCs were identified in only 8.7% of CTCs. Conclusions CD47 expression is identified in the great majority of CTCs in mBC and could represent a potent signal to facilitate the escape from innate immune response. PD-L1 expression on CTCs is less commonly observed and could serve for the attenuation of an adaptive anti-tumor immune response. Interestingly, CD47 and PD-L1 are co-expressed in a subset of CTCs, whereas simultaneous high expression on single CTCs is even less common. The expression of these molecules is currently further investigated in a larger cohort of patients with mBC and in patients with early disease, in order to evaluate their differential distribution that potentially reflects the equilibrium and/or escape from the immune surveillance. Citation Format: Mavroudis D, Papadaki MA, Tsoulfas PG, Troullinou K, Apostolopoulou CA, Papadaki C, Agelaki S. Co-expression of molecules associated with innate and adaptive immune response on single CTCs of patients with metastatic breast cancer (mBC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-01-13.

METTL3 regulates viral m6A RNA modification and host cell innate immune responses during SARS-CoV-2 infection.

Towards addressing questions related to HIV pathogenesis and vaccine design we are fortunate to have the availability of the SIV-infected rhesus macaque model. The strengths of this model which include a rapid rate of progression to AIDS and knowledge of the dose route and strain of the infecting virus complement studies in HIV-infected patients in which the reagents host genetics and access to samples are more extensive and better defined. Unfortunately there is currently still too little known about the antiviral immune responses in either system to directly and accurately compare their similarities and differences and to draw any definitive conclusions. Therefore the data and views presented herein will simply reflect what has recently been discovered in both humans and non-human primate studies. (excerpt)