Research progress of interaction between peste des petits ruminants virus and host cells / 中国生物制品学杂志

@#Peste des petits ruminants(PPR)is a highly contagious disease with high mortality which is caused by peste des petits ruminants virus(PPRV)infection and leads to enormous economic losses for sheep husbandry both at home and abroad. The knowledge of interactions between PPRV and host cells is the basis of understanding of the pathogenesis and the prerequisite of disease prevention and control. This paper reviews the studies on the activation of host innate immune response by PPRV infection,the immune evasion of PPRV mediated by viral protein products,and the induction of apoptosis,autophagy and inflammasome resistance to virus,which provides a reference for further discussion on the immune evasion of PPRV and the key nodes involved in the interaction between PPRV and the host,thus providing theoretical guidance for effective prevention and control of PPR transmission.

Discussion on the mechanism of Yanghe Decoction in treating chronic osteomyelitis based on network pharmacology and molecular docking / 国际中医中药杂志

Objective:To study the active components and their potential mechanism of Yanghe Decoction for the treatment of chronic osteomyelitis (CO) via the methods of network pharmacology and molecular docking.Methods:Active components and action targets of Yanghe Decoction were screened from TCMSP, BATMAN-TCM and relevant literature. GeneCards, OMIM, DisGeNET, and PharmGKB databases were used to predict the targets for the CO. Cytoscape 3.8.0 software and STRING database were used to build the networks of "Chinese materia medica-active components-potential targets" and "protein-protein interaction", and according to topological parameters in the network, the core active components as well as Hub genes were screened. MCODE plug was used to accomplish clustering analysis of protein modules in PPI network. Then, intersection targets were enriched and analyzed by GO and KEGG in KOBAS database. Finally, molecular docking was carried out with the help of Autodock tool platform to predict the binding ability between the main active components and key targets.Results:A total of 120 active components of Yanghe Decoction and 402 targets were obtained; 1 464 CO-related targets were screened, and there were 103 intersection target genes of Yanghe Decoction-CO, 110 active components related to intersection targets, which mainly contained some flavonoids and Phytosterols, such as quercetin, Kaempferol, and Beta-Sitosterol. There were 9 Hub genes, including TNF, IL6, AKT1, etc., and 4 protein modules which involved the regulation of immune inflammatory response, vascular microcirculation, bone development, and formation, material synthesis and metabolism and other physiological processes. 193 signaling pathways and 1 552 GO results were acquired in KOBAS database. Molecular docking results showed that the active compounds had good binding activity with key targets based on the minimum binding energy of less than - 5 kcal/mol.Conclusion:The mechanism in the treatment of CO with Yanghe Decoction is a complex process of multiple components, multiple targets, and multiple pathways. It mainly regulates targets such as TNF, IL-6, CXCL8, VEGFA, and AKT1 through pathways such as TNF signaling pathway, IL-17 signaling pathway, and Toll-like receptors, participating in local inflammatory reactions, microcirculation, and bone cell metabolism in chronic osteomyelitis, and interfering with the immune escape mechanism of pathogenic bacteria.

The action mechanism of glioblastoma cell-derived exosome: a review / 生物工程学报

Patients with glioblastoma (GBM) generally have a bad prognosis and short overall survival after being treated with surgery, chemotherapy or radiotherapy due to the histological heterogeneity, strong invasive ability and rapid postoperative recurrence of GBM. The components of GBM cell-derived exosome (GBM-exo) can regulate the proliferation and migration of GBM cell via cytokines, miRNAs, DNA molecules and proteins, promote the angiogenesis via angiogenic proteins and non-coding RNAs, mediate tumor immune evasion by targeting immune checkpoints with regulatory factors, proteins and drugs, and reduce drug resistance of GBM cells through non-coding RNAs. GBM-exo is expected to be an important target for the personalized treatment of GBM and a marker for diagnosis and prognosis of this kind of disease. This review summarizes the preparation methods, biological characteristics, functions and molecular mechanisms of GBM-exo on cell proliferation, angiogenesis, immune evasion and drug resistance of GBM to facilitate developing new strategies for the diagnosis and treatment of GBM.

Long COVID-19 syndrome associated with Omicron XBB.1.5 infection: a case report

BACKGROUND There is interest in lingering non-specific symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, referred to as Long coronavirus disease 2019 (Long COVID-19). It remains unknown whether the risk of Long COVID-19 is associated with pre-existing comorbidities or initial COVID-19 severity, including infections due to new Omicron lineages which predominated in 2023. OBJECTIVES The aim of this case report was to characterize the clinical features of acute XBB.1.5 infection followed by Long COVID-19. METHODS We followed a 73-year old female resident of Rio de Janeiro with laboratory-confirmed SARS-CoV-2 during acute infection and subsequent months. The SARS-CoV-2 lineage was determined by genome sequencing. FINDINGS The participant denied comorbidities and had completed a two-dose vaccination schedule followed by two booster doses eight months prior to SARS-CoV-2 infection. Primary infection by viral lineage XBB.1.5. was clinically mild, but the participant subsequently reported persistent fatigue. MAIN CONCLUSIONS This case demonstrates that Long COVID-19 may develop even after mild disease due to SARS-CoV-2 in fully vaccinated and boosted individuals without comorbidities. Continued monitoring of new SARS-CoV-2 lineages and associated clinical outcomes is warranted. Measures to prevent infection should continue to be implemented including development of new vaccines and antivirals effective against novel variants.

Exploration of Immune Tolerance and Treatment for Esophageal Cancer / 肿瘤防治研究

Monoclonal antibody drugs that inhibit programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) have been widely used in esophageal cancer (EC) and yielded significant therapeutic responses. However, only a few patients obtain lasting clinical benefits due to primary or acquired drug resistance, and new treatment schemes are urgently needed. The tumor immune microenvironment is the main factor that affects patients' response to immunosuppressive agents. This article will discuss the role of immunosuppressive cells and non-cellular components in the immune process to provide ideas for the next research direction of EC.

Bispecific prodrug nanoparticles circumventing multiple immune resistance mechanisms for promoting cancer immunotherapy

Cancer immunotherapy is impaired by the intrinsic and adaptive immune resistance. Herein, a bispecific prodrug nanoparticle was engineered for circumventing immune evasion of the tumor cells by targeting multiple immune resistance mechanisms. A disulfide bond-linked bispecific prodrug of NLG919 and JQ1 (namely NJ) was synthesized and self-assembled into a prodrug nanoparticle, which was subsequently coated with a photosensitizer-modified and tumor acidity-activatable diblock copolymer PHP for tumor-specific delivery of NJ. Upon tumor accumulation via passive tumor targeting, the polymeric shell was detached for facilitating intracellular uptake of the bispecific prodrug. NJ was then activated inside the tumor cells for releasing JQ1 and NLG919 via glutathione-mediated cleavage of the disulfide bond. JQ1 is a bromodomain-containing protein 4 inhibitor for abolishing interferon gamma-triggered expression of programmed death ligand 1. In contrast, NLG919 suppresses indoleamine-2,3-dioxygenase 1-mediated tryptophan consumption in the tumor microenvironment, which thus restores robust antitumor immune responses. Photodynamic therapy (PDT) was performed to elicit antitumor immunogenicity by triggering immunogenic cell death of the tumor cells. The combination of PDT and the bispecific prodrug nanoparticle might represent a novel strategy for blockading multiple immune evasion pathways and improving cancer immunotherapy.

The interaction between 2019-nCoV and interferon Ⅰ / 中华临床感染病杂志

COVID-19 has swept across the world, causing widespread epidemics and millions of life lost worldwide. After infected with 2019-nCoV, the body quickly mobilizes the innate immune response and produces type Ⅰ interferon (IFN-Ⅰ). IFN-Ⅰ plays an important role in virus clearance in the early stage of disease. This article reviews the innate immune recognition after virus infection and the interaction between 2019-nCoV and IFN-Ⅰ, which would be conductive to understanding the pathogenesis and antiviral treatment of COVID-19.

Advances in research on tumor immunotherapy and its drug development / 中国药科大学学报

@#The progress of molecular biology and tumor biology has greatly changed the mode of cancer treatment. A large number of scientific studies have revealed the mechanism of tumor immune evasion, and a variety of new types of tumor immunotherapy have emerged, which has become another effective treatment of cancer after surgery, radiotherapy, chemotherapy and targeted therapy. This paper introduces the mechanism of tumor cell immune evasion, and focuses on the design principle, biological drugs and the latest research progress of immunotherapy, such as cytokine immunotherapies, therapeutic monoclonal antibody immunotherapy, PD-1/PD-L1 therapy, CAR-T therapy, tumor vaccine, oncolytic virus and so on. At the same time, the advantages and disadvantages of various immunotherapies are compared to provide reference for drug research and development in tumor immunotherapy.

Respuesta inmune disfuncional en pacientes con COVID-19. ¿Qué nos dice la evidencia? / Dysfunctional immune response in COVID-19 patients. What does the evidence tell us?

In December 2019 a novel coronavirus (SARS-CoV-2) was identified in Wuhan, China, and became rapidly the worst pandemic in 100 years. Coronaviruses are respiratory viruses that can cause diseases ranging from mild to fatal lower respiratory tract infections. In a fraction of the affected patients, coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, can lead to acute respiratory distress syndrome (ARDS) and intensive care unit (ICU) admission, both associated with high mortality. To date, the existing evidence suggests a leading role of the immune system in the pathogenesis of severe COVID-19, including mechanisms associated with hyperinflammation, immune evasion, cytokine release syndrome, depletion of functional T cells, and ineffective humoral immunity. Here we discuss the current evidence regarding these findings.

Expression of PD-L1 in triple negative breast cancer tissues and its relationship with angiogenesis / 中国肿瘤生物治疗杂志

@# Objective: To investigate the expressions of programmed death ligand 1（PD-L1）in triple-negative breast cancer (TNBC) and its correlation with angiogenesis. Methods: 120 cases of TNBC patients who underwent surgery in the Fourth Hospital of Hebei Medical University from March 1, 2011 to June 1, 2012 were collected. The tumor tissues of patients were surgically resected and confirmed by pathology. PD-L1 protein expression in TNBC tissues of 120 patients was detected by tissue microarray combined with immunohistochemistry, and its relationship with various clinical indicators was analyzed. Blood vessels and lymphatic vessels were labeled withCD34andD2-40todetectmicrovesseldensity(MVD)andlymphaticvesseldensity(LVD)inTNBC.Results:Thepositiveexpression rate of PD-L1 in the tumor cells and interstitial infiltrating lymphocytes fromTNBC was 56.7% (68/120); No correlation was found between PD-L1 protein expression and the gender, age, histological grade, clinical stage, or tumor size of patients with TNBC (P>0.05), but related to the lymph node metastasis (P<0.05) and vascular thrombus (P<0.05). TNBC with high PD-L1 expression exhibited high incidence of lymph node metastasis and formation of vascular thrombus, and the expression of PD-L1 was positively correlated with MVD (r=0.500, P=0.02) as well as LVD (r=0.662, P=0.01). Log-Rank test showed that the survival time of TNBC patients with positive PD-L1 protein expression was significantly shorter than that of patients with negative expression (P<0.05). Cox multivariate analysis suggested that PD-L1 protein expression could be an independent prognostic factor for TNBC overall survival. Conclusion: PD-L1 plays an important role in TNBC angiogenesis and lymphangiogenesis, and is closely related to TNBC invasion and metastasis; blocking PD1/PD-L1 signal pathway is expected to be an effective new strategy for TNBC treatment.

Klotho protein inhibits Treg/TH17 cell-mediated immune escape of cervical cancer cells by regulating TGF-β1/Foxp3/RORγt signaling pathway / 中国肿瘤生物治疗杂志

@#Objective: To study the effect of anti-aging Klotho protein on immune escape mediated by regulatory T cells (Treg)/helper T cells 17 (TH17) in mice bearing cervical cancer and its mechanism. Methods: The model of cervical cancer-bearing mice were established, and the control group (normal mice), model group (cervical cancer-bearing mice model), and Klotho treatment group (cervical cancer-bearing mice treated with Klotho protein, 200 ng/d) were set up. The weight of cervical cancer tumors in mice of each group was weighed at 7 and 14 days after treatment respectively, PBMCs were separated at the same time. Flow cytometry was used to detect the changes of T lymphocyte function and the proportion of Treg and TH17 cells in mice. qPCR was used to detect the expressions of Foxp3 and RORγt, the key transcription factors of Treg/TH17 cells, in PBMCs of mice in each group. The changes of IL-17, IL-6, IL10, TGF-β and IL-23 in PBMCs were detected by ELISA. The protein expressions of Klotho, TGF-β, Foxp3 and RORγt in PBMCs of mice were detected by WB assay. Results: On the 14th day, the tumor inhibition rate of the cervical cancer-bearing mice in the Klotho group was significantly higher than that in the Model group [(52.16±8.25)% vs (23.33±6.29)% the model group to be supplemented, P< 0.05). Compared with the Control group, the ratios of Treg and TH17 cells in the lymphocytes of the tumor-bearing mice significantly increased (all P<0.05), the ratios of total T lymphocytes (CD3+), auxiliary/induced T lymphocytes (CD3+CD4+) and immune index (CD3+CD4+/CD3+CD8+ cells) decreased significantly (all P<0.05); in addition, the mRNAexpressions of Foxp3 and RORγt genes, cytokines of IL-17, IL-6, IL-10, TGF-β and IL-23, as well as protein expressions of TGF-β1, Foxp3 and RORγt increased significantly (all P <0.05), while the level of Klotho protein significantly decreased in Model group (P<0.05). Compared with the Model group, the above indicators showed opposite changes in Klotho group (P<0.05), but there was no significant difference with the Control group (all P> 0.05). Conclusion: Klotho protein may inhibit Treg/TH17 cell-mediated immune evasion in cervical cancer-bearing mice by inhibiting TGF-β1/Foxp3/RORγt signaling pathway and exert anti-tumor effect.

Progress in studies on mechanism of immune evasion of Epstein-Barr virus / 中华实验和临床病毒学杂志

Epstein-Bar virus (EBV) infection is widespread within the human population with over 95% of adults being infected. In response to primary EBV infection, the host mounts an antiviral immune response comprising both innate and adaptive immune system. In healthy populations, the immune system can control EBV infection to a large extent. However, the virus cannot be cleared. Instead, EBV establishes a persistent latent infection in B lymphocytes characterized by limited viral gene expression. To establish a persistent infection efficiently, EBV have evolved a number of strategies to avoid immune elimination. In this review, we focus on the immune evasion mechanisms of EBV encoded immune-evasion proteins, microRNA and host exosome pathway.

Immune status of pancreatic cancer patient and progress in immunotherapy / 肿瘤

With the 5-year survival rate of just 8%, the prognosis of pancreatic cancer (PC) is poor, and PC is projected to be the second leading cause of cancer deaths by 2030. Most PC patients are not eligible for surgery upon diagnosis owing to the difficulty in early diagnosis; moreover, PC is resistant to chemotherapy and radiation. Accordingly, it's time to emphasize a need for more effective therapies. As an alternative, immune modulating strategies have recently achieved success in melanoma. Although the state of immunologic tolerance must be reversed in the tumor microenvironment before this therapeutic approaches gain success. In the last decade, the knowledge of PC immune microenvironment has advanced considerably, which builds the basis for immune modulating strategies. In this review, the evolution of the cancer immunology in PC is discussed, and the strategies employing immune modulation in PC is also reviewed.

Research advances in immune evasion mechanism of helminths / 中国人兽共患病学报

Helminth infection can lead to organic,digestive and other tissue's pathological damage.Helminth diseases are harmful to human and animal health,and can cause reproductive failure,inhibits the growth and development of juvenile ani-mals,even lead to death of humans and animals in serious cases,and poses significant impacts on public health and causes eco-nomic losses to the animal husbandry.Currently,the prevention and control of helminth disease is largely dependent on inte-grated control measures including the use of drugs.Due to drug residues,drug resistance,and other issues,the development of new drugs and vaccines is imminent.So far,there is few ideal vaccines to control helminth diseases,which is due to that hel-minths have evolved mechanisms to evade host immune attacks during evolution,such as immune isolation,antigen variation, molecular simulation and so on.Therefore,this review describes the recent research advances in the immune evasion strategies of parasitic helminth,which aims to provide a reference for the development of new vaccines or drugs for better prevention and control of helminth diseases.

Resposta imune e mecanismos de evasão na carcinogênese de lábio: um estudo imunoistoquímico / Immune response and evasion mechanisms in lip carcinogenesis: an immunohistochemical study

A vigilância imunológica, principalmente mediada por linfócitos T CD8+ , reconhece e destrói células malignas ou alteradas. Contudo, através de estratégias imunossupressoras, como as vias de sinalização do ligante de morte celular programada-1 (PD-L1) e do antígeno leucocitário humano-G (HLA-G), estas células mutadas conseguem escapar da resposta imune antitumoral. Este estudo investigou a imunoexpressão de PD-L1, HLA-G, CD8 e granzima B (GrB) no microambiente de carcinomas de células escamosas (CCEs) de lábio (n = 40), de queilites actínicas (QAs; n = 55) e de mucosa labial saudável (MLS; n = 10). As amostras foram submetidas à técnica da imunoistoquímica e as análises das imunomarcações seguiram métodos semi-quantitativos (PD-L1 e HLA-G) e quantitativos (CD8 e GrB). A expressão das proteínas foi comparada entre os três grupos de amostras, bem como com parâmetros clinicopatológicos das lesões e sobrevida global dos pacientes com CCE de lábio. A correlação entre as proteínas e o tipo do microambiente tumoral de acordo com a presença de PD-L1 e CD8 também foram avaliados. Os testes estatísticos incluíram o exato de Fisher, Mann-Whitney, Kruskal-Wallis, correlação de Spearman e log-rank para comparação das curvas de sobrevida global construídas pelo método Kaplan-Meier. O nível de significância foi estabelecido em 5%. Os números de células CD8+ e GrB+ aumentaram progressivamente de MLS para CCEs de lábio, com QAs exibindo números intermediários (p < 0,01). A menor expressão dessas proteínas foi associada à metástase para linfonodos e tumores pobremente diferenciados (p < 0,05). A expressão de PD-L1 e HLA-G em células neoplásicas/ceratinócitos e estroma/tecido conjuntivo foi significativamente maior em CCEs de lábio e QAs, em comparação com MLSs (p < 0,05). PDL1 não foi significativamente associado aos aspectos clinicopatológicos das lesões. A maioria dos CCEs de lábio mostrou coexistência de células PD-L1+ e CD8+ (72,5%) no microambiente tumoral. A expressão de PD-L1 foi diretamente correlacionada à infiltração linfocítica CD8+ e GrB+ em CCEs de lábio (p < 0,05). A expressão das proteínas não foi associada com a sobrevida global dos pacientes com CCEs de lábio (p > 0,05). Nossos achados sugerem que as moléculas imunossupressoras PD-L1 e HLA-G estão consistentemente expressas desde QAs e se mantém até fases avançadas dos CCE de lábio. A correlação entre a expressão de PD-L1 e a expressão de CD8 e GrB nos carcinomas sugere que PD-L1 pode surgir como um mecanismo de escape frente a uma resposta antitumoral ativa (AU).

Immune surveillance, mainly mediated by CD8 + T lymphocytes, recognize and destroy malignant or altered cells. However, through immunosuppressive strategies, such as the signaling pathways of the programmed cell death ligand-1 (PD-L1) and human leukocyte antigen-G (HLA-G), these mutated cells often escape the antitumor immune response. The aim of this study was to investigate and compare the immunoexpression of PD-L1, HLA-G, CD8 and granzyme B (GrB) in the microenvironment of lip squamous cell carcinomas (LSCCs; n = 40), actinic cheilitis (ACs; n = 55), and healthy lip mucosa (HLM; n = 10). The samples were submitted to immunohistochemistry and the analysis followed a semi-quantitative (PD-L1 and HLA-G) and quantitative methods (CD8 and GrB). Protein expression was compared between the three groups of samples, as well as with the lesion's clinicopathologic parameters and overall survival of patients with LSCC. Correlation between proteins and the type of tumor microenvironment according to a presence of PD-L1 and CD8 were also evaluated. Statistical tests included Fisher's exact, Mann-Whitney, Kruskal-Wallis, Spearman's correlation, as well as the log-rank for comparison of the overall survival built through Kaplan-Meier method. Significance was set at p < 0.05. The CD8+ and GrB+ cell numbers progressively increased from HLMs to LSCCs, with ACs exhibiting intermediate numbers (p < 0.01). Lower expression of these proteins was associated with lymph node metastasis and poor tumor differentiation (p < 0.05). PD-L1 and HLA-G expression in neoplastic cells/keratinocytes and stroma/connective tissue was significantly higher in LSCCs and ACs, compared to HLMs (p < 0.05). PD-L1 was not significantly associated with clinicopathological aspects of the lesions. Most LSCCs showed coexistence of PD-L1+ and CD8+ cells (72.5%) in the tumor microenvironment. PDL1 was directly correlated to CD8+ and GrB+ lymphocytic infiltration in LSCCs (p < 0.05). Proteins expression was not associated with overall survival of LSCCs patients (p > 0.05). Our findings suggest that immunosuppressive molecules PD-L1 and HLA-G are consistently expressed from ACs and are maintained until advanced stages of LSCCs. The correlation between PD-L1 expression and the expression of CD8 and GrB in carcinomas suggests that that PD-L1 may appear as an escape mechanism against an active antitumor response (AU).

Purification of monoclonal anti-B7-H4 antibody and the blockade of B7-H4-mediated tumor immune evasion by the antibody / 中国药科大学学报

The purified 3C8 was obtained by two step column purification,including Protein G affinity purification and DEAE anion exchange purification.The purity of purified 3C8 was about 93％ when analyzed by reverse column.SDS-PAGE showed that the purity of 3C8 was increased greatly by two step purification.By flowcytometry we found that 3C8 specifically binded with B7-H4/293T cells and did not bind with Mock/293T cells,moreover 3C8 did not bind with other B7 family members transgene cells.In confocal experiment 3C8 could specifically stained B7-H4/293T cells.In Western blot only B7-H4/293T cells showed positive band while Mock/293T cells showed negative result.The result of immunohistochemistry showed that B7-H4 was highly expressed in prostate cancer and renal cell carcinoma,while para-cancer tissues did not express B7-H4.The T cell proliferation experiment showed that B7-H4-Ig could bind to activate T cells and inhibit T cell proliferation,while 3C8 could block the binding of B7-H4-Ig and reverse the T cell proliferation inhibition effect of B7-H4-Ig by CFSE and CCK8 assay.The cytokine IFN-γ and IL-2 secreted by activating T cells was decreased by B7-H4-Ig and 3C8 could reverse the effect of B7-H4-Ig.

The latent infection of HSV-1 and stress-induced reactivation / 中国药理学通报

Herpes simplex virus type Ⅰ(HSV-1) is a common pathogen, and human is the only natural host of it.Following a period of lytic replication in epithelial cells, HSV-1 enters axon terminals of sensory neurons and then travels via retrograde transport to the sensory ganglia where latency can be established.Upon the stimulation of some stressors, the latent virus can reactivate, leading to recurrent diseases.Therefore, to clarify the mechanism of HSV-1 latent infection and stress-induced reactivation will offer new insights into the prevention, treatment and control of HSV-1 infection.In this review, we describes the mechanisms underlying HSV-1 latent infection and stress-induced reactivation.

Advance in Herpesvirus US10 gene and its encoded protein / 中国人兽共患病学报

US10 gene of Herpesvirus is located in the short unique region of its genome and not essential for virus replication.US10 gene encodes a phosphorylated tegument-capsid associated protein or type Ⅰ transmembrane glycoprotein which selectively targets the cytoplasmic tail of HLA-G,a kind of nonclassical class Ⅰ MHC molecular,to reduce and block the host NK cell cytotoxicity in immune evasion.US10 can also interact with host proteins to play a pathogenic role and regulate the expression of other viral proteins such as glycoprotein E (gE).Through further research,the role of US10 in virulence and its ability to combine with RNA and regulate transcription can be judged in the future.

Immunodetection of myeloid and plasmacytoid dendritic cells in mammary carcinomas of female dogs / Imunodetecção de células dendríticas mieloides e plasmocitoides nos carcinomas mamários em cadelas

Dendritic cells have attracted great interest from researchers as they may be used as targets of tumor immune evasion mechanisms. The main objective of this study was to evaluate the relationship between the dendritic cells (DCs) subpopulation in simple type mammary carcinomas in female dogs. Two groups of samples were used: the control group consisted of 18 samples of mammary tissue without changes and the tumor group with 26 simple type mammary carcinomas. In these groups, we evaluated the immunodetection of immature and mature myeloid DCs, plasmacytoid DCs and MHC-II. In mammary tumor, mature myeloid DCs predominated in the peritumoral region, while immature myeloid DCs and plasmacytoid DCs were evident in the intratumoral region. Immunostaining of MHC-II was visualized in mammary acini (control group), in tumor cells and inflammatory infiltration associated with tumors. The comparison between the control and tumor groups showed a statistically significant difference between immature myeloid DCs, mature myeloid DCs and plasmacytoid DCs. The immunodetection of MHC-II was not significant when comparing the groups. The predominance of immature DCs in the tumor group is possibly related to an inefficient immune response, promoting the development and survival of tumor cells. The presence of plasmacytoid DCs in the same group suggests a worse prognosis for female dogs with mammary tumors. Therefore, the ability of differentiation of canine dendritic cells could be influenced by neoplastic cells and by the tumor microenvironment...

As células dendríticas têm despertado grande interesse dos pesquisadores, pois podem ser alvo dos mecanismos de evasão imune do tumor. O objetivo principal deste estudo foi avaliar a relação entre as subpopulações de células dendríticas (DCs) nos carcinomas mamários do tipo simples em cadelas. Dois grupos de amostras foram utilizados, o grupo controle composto por 18 amostras de tecido mamário sem alterações e o grupo tumor com 26 carcinomas mamários do tipo simples. Nestes grupos foram avaliadas a imunodetecção de DCs mieloides imaturas e maduras, DCs plasmocitoides e de MHC-II. Nas mamas com tumor, as DCs mieloides maduras predominaram na região peritumoral, enquanto que as DCs mieloides imaturas e as DCs plasmocitoides foram evidentes na região intratumoral. A imunomarcação do MHC-II foi visualizada nos ácinos mamários (grupo controle), nas células tumorais e no infiltrado inflamatório associado aos tumores. Na comparação entre os grupos controle e tumor houve diferença estatística significativa entre as DCs mieloides imaturas, DCs mieloides maduras e DCs plasmocitoides. A imunodetecção de MHC-II não foi significativa na comparação entre os grupos. A predominância de DCs imaturas no grupo tumor, possivelmente, está relacionada com uma resposta imune ineficiente, favorecendo o desenvolvimento e a sobrevivência das células tumorais. A presença das DCs plasmocitoides no mesmo grupo sugere um prognóstico pior para cadelas com tumores de mama. Portanto, a capacidade de diferenciação das células dendríticas caninas poderia ser influenciada pelas células neoplásicas e pelo microambiente tumoral...

Evasión de la respuesta inmune por virus herpes simplex / Immune evasion by herpes simplex viruses

Herpes simplex viruses and humans have co-existed for tens of thousands of years. This long relationship has translated into the evolution and selection of viral determinants to evade the host immune response and reciprocally the evolution and selection of host immune components for limiting virus infection and damage. Currently there are no vaccines available to avoid infection with these viruses or therapies to cure them. Herpes simplex viruses are neurotropic and reside latently in neurons at the trigeminal and dorsal root ganglia, occasionally reactivating. Most viral recurrences are subclinical and thus, unnoticed. Here, we discuss the initial steps of infection by herpes simplex viruses and the molecular mechanisms they have developed to evade innate and adaptive immunity. A better understanding of the molecular mechanisms evolved by these viruses to evade host immunity should help us envision novel vaccine strategies and therapies that limit infection and dissemination.

Los virus herpes simplex y humanos co-existen desde decenas de miles de años. Esta prolongada relación se ha traducido en la evolución y selección de determinantes virales para evadir la respuesta inmune y recíprocamente la evolución y selección de componentes inmunes del hospedero para limitar la infección viral y el daño que producen. Actualmente no existen vacunas para evitar la infección de estos virus o terapias que la curen. Los virus herpes simplex son neurotrópicos y permanecen latentes en neuronas de ganglios trigémino y dorsales, reactivándose esporádicamente. La mayoría de las recurrencias por virus herpes simplex son sub-clínicas y por tanto pasan inadvertidas. Aquí discutimos los pasos iniciales de la infección porvirus herpes simplex y los mecanismos moleculares que estos virus han desarrollado para evadir la respuesta inmune innata y adaptativa. Una mejor comprensión de los mecanismos moleculares evolucionados por estos virus para evadir la respuesta inmune del hospedero deberían ayudarnos visualizar nuevas estrategias para desarrollar vacunas y terapias que limiten su infección y diseminación.