Clinical and mechanistic insights into Brucella and viral co-infection.

Transient global amnesia with unexpected clinical and radiological findings: A case series and systematic review

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

Typical symptoms of Ramsay Hunt syndrome (RHS) consist of painful vesicular eruptions in the external ear, unilateral facial palsy, and/or vestibulocochlear deficit. When RHS patients show atypical clinical manifestations, correct diagnosis can be delayed, and ideal treatment timing for antiviral therapy may be missed. The aim of this study is to describe RHS patients with atypical clinical manifestations and evaluate the usefulness of magnetic resonance imaging (MRI) for early differential diagnosis. We retrospectively reviewed the clinical data and investigated the findings of internal auditory canal (IAC) MRI of seven patients diagnosed with RHS presenting "atypical" clinical manifestations between January 2013 and December 2016. "Typical" symptoms of RHS consist of herpetic vesicular eruption and facial palsy with or without vestibulocochlear deficit. Regardless of symptomatic presentations, IAC MRI demonstrated post-contrast enhancement of cranial nerve (CN) VII, CN VIII, and IAC dura in patients with atypical clinical manifestations. In cases with multiple lower CN palsy, enhancement along the involved nerve was observed on IAC MRI. When RHS was complicated by acute parotiditis, diffuse enhancement of the parotid gland was demonstrated. The present study shows that in IAC MRI of RHS patients with atypical clinical manifestations, post-contrast enhancement was not confined to the facial nerve but also observed in CN VIII and IAC dura regardless of the symptoms, which may facilitate early diagnosis of RHS.

Objective To analyze the atypical clinical manifestations and clinical prognosis of pediatric diffuse intrinsic pontine glioma (DIPG). Methods A total of 27 patients with complete clinical data of DIPG undergoing clinical treatment at Neurosurgery Department of Beijing Tiantan Hospital, Capital Medical University from November 2015 to November 2017 were retrospectively enrolled into this study. All patients were divided into 2 groups according to the presence of atypical manifestations: atypical clinical manifestation group (17 cases) and the control group (10 cases). Among the 27 cases, 16 patients underwent stereotactic biopsy or open cranial biopsy, and the other 11 patients underwent tumor excision through craniotomy. All the children were followed up clinically or by telephone after operation to study the clinical outcomes. Comparative analysis was conducted on those clinical data. Prognosis was compared between the 2 groups through Kaplan-Meier survival analysis. Results Among the 27 cases, 20 were pathologically identified as high grade gliomas (including 4 cases of diffuse midline glioma, 6 cases of glioblastoma, 6 cases of anaplastic oligoastrocytoma, 4 cases of anaplastic astrocytoma) and 7 as low grade glioma (including 4 cases of oligoastrocytoma and 3 cases of astrocytoma). One child suffered from pneumonia and finally recovered postoperatively. No statistically significant difference (all P>0.05) was identified between 2 groups in the age, gender, clinical manifestation (including cranial nerve palsy, long tract dysfunction and cerebellum signs), clinical imaging features (including lesion enhancement, supratentorial ventricle enlargement and brachium pontis involvement), clinical treatment or pathology. Kaplan-Meier survival analysis showed that patients with atypical clinical manifestation had significantly higher cumulative survival rate than those in the control group (P=0.045). Conclusion Atypical clinical manifestation could be identified in some pediatric DIPG patients, which might be predictive of a better prognosis. Key words: Brainstem tumor; Child; Atypical clinical manifestation

Multi-omic Analyses Reveal Complex Interactions Between HCVand Hepatocytes Demonstrating That the Red Queen IsUpand Running.

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

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

Editorial overview: Autoimmunity

The most common anatomic sites affected by extrapulmonary tuberculosis are lymph nodes, pleura, bones, and joints, urogenital tract, and meninges. Tuberculous arthritis is difficult to diagnose early because of its atypical insidious clinical manifestations and non-specific imaging findings. A 59-year-old male presented with progressive swelling in his left knee for over two months. The patient was initially misdiagnosed with pigmented villonodular synovitis (PVNS) and had undergone total knee arthroplasty (TKA) two years ago, however, the TKA did not completely alleviate his symptoms. Comprehensive radiological and laboratory assessments, including X-rays, magnetic resonance imaging and computed tomography scans, and an interferon-γ release assay (IGRA), pointed towards a diagnosis of tuberculous knee arthritis. Definitive diagnosis was established through the detection of Mycobacterium tuberculosis (MTB) DNA in the synovial fluid via polymerase chain reaction (PCR) and a positive IGRA result. The case underscores the importance of considering MTB infection in the differential diagnosis of chronic unilateral knee arthritis, especially given the atypical clinical manifestations and imaging findings that can mimic other conditions like PVNS.

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.

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.

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.

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

Gene Therapy Research at the Frontiers of Viral Immunology