A bird's eye view on the role of dendritic cells in SARS-CoV-2 infection: Perspectives for immune-based vaccines

Coronavirus disease-19 (COVID-19) is a complex disorder caused by the pandemic diffusion of a novel coronavirus named SARS-CoV-2. Clinical manifestations vary from silent infection to severe pneumonia, disseminated thrombosis, multi-organ failure, and death. COVID-19 pathogenesis is still not fully elucidated, while increasing evidence suggests that disease phenotypes are strongly related to the virus-induced immune system's dysregulation. Indeed, when the virus-host cross talk is out of control, the occurrence of an aberrant systemic inflammatory reaction, named “cytokine storm,” leads to a detrimental impairment of the adaptive immune response. Dendritic cells (DCs) are the most potent antigen-presenting cells able to support innate immune and promote adaptive responses. Besides, DCs play a key role in the anti-viral defense. The aim of this review is to focus on DC involvement in SARS-CoV-2 infection to better understand pathogenesis and clinical behavior of COVID-19 and explore potential implications for immune-based therapy strategies

Dendritic Cells Are the Intriguing Players in the Puzzle of Idiopathic Pulmonary Fibrosis Pathogenesis

Idiopathic pulmonary fibrosis (IPF) is the most devastating progressive interstitial lung disease that remains refractory to treatment. Pathogenesis of IPF relies on the aberrant cross-talk between injured alveolar cells and myofibroblasts, which ultimately leads to an aberrant fibrous reaction. The contribution of the immune system to IPF remains not fully explored. Recent evidence suggests that both innate and adaptive immune responses may participate in the fibrotic process. Dendritic cells (DCs) are the most potent professional antigen-presenting cells that bridge innate and adaptive immunity. Also, they exert a crucial role in the immune surveillance of the lung, where they are strategically placed in the airway epithelium and interstitium. Immature DCs accumulate in the IPF lung close to areas of epithelial hyperplasia and fibrosis. Conversely, mature DCs are concentrated in well-organized lymphoid follicles along with T and B cells and bronchoalveolar lavage of IPF patients. We have recently shown that all sub-types of peripheral blood DCs (including conventional and plasmacytoid DCs) are severely depleted in therapy naïve IPF patients. Also, the low frequency of conventional CD1c+ DCs is predictive of a worse prognosis. The purpose of this mini-review is to focus on the main evidence on DC involvement in IPF pathogenesis. Unanswered questions and opportunities for future research ranging from a better understanding of their contribution to diagnosis and prognosis to personalized DC-based therapies will be explored

Circulating dendritic cells are severely decreased in idiopathic pulmonary fibrosis with a potential value for prognosis prediction

Dendritic cells (DCs) accumulate in the lung of patients affected by idiopathic pulmonary fibrosis (IPF). We measured the frequencies of circulating conventional CD1c + and CD141+ cells (namely, cDC2 and cDC1) and of plasmacytoid CD303+ DCs in a cohort of 60 therapy naive IPF patients by flow cytometry. Peripheral levels of reactive oxygen species (ROS) and of pro-inflammatory and Th1/Th2 polarizing cytokines were also analyzed. All blood DC subtypes were significantly reduced in IPF patients in comparison to age- and sex-matched controls, while ROS and interleukin (IL-6) levels were augmented. IL-6 expression increased along with disease severity, according to the gender-age-physiology index, and correlated with the frequency of cDC2. IL-6 and cDC2 were not influenced by anti-fibrotic therapies but were associated with a reduced survival, the latter being an independent predictive biomarker of worse prognosis. Deciphering the role of DCs in IPF might provide information on disease pathogenesis and clinical behavior

Measles: An overview of a re-emerging disease in children and immunocompromised patients

Despite the availability of a safe and effective vaccine, in 2018, around 350,000 measles cases were reported worldwide, which resulted in an estimate of 142,300 deaths from measles. Additionally, in 2017, global measles cases spiked, causing the death of 110,000 people, mostly children under the age of 5 years and immunocompromised adults. The increase in measles incidence is caused by the ongoing reduction of vaccination coverage. This event has triggered public and scientific interest. For this reason, we reviewed the pathophysiology of measles infection, focusing on mechanisms by which the virus spreads systemically through the host organism. By reaching the lymphocytes from the airways through a \u201ctrojan horse\u201d strategy, measles induces an immunosuppression status. H and F glycoproteins, both expressed in the envelope, ensure attachment of the virus to host cells and spreading from one cell to another by binding to several receptors, as described in detail. The severity of the disease depends both on the age and underlying conditions of patients as well as the social and health context in which epidemics spread, and is often burdened by sequelae and complications that may occur several years after infection. Particular attention was paid to special groups that are more susceptible to severe or atypical measles. An overview of microbiology, symptoms, diagnosis, prevention, and treatment completes and enriches the review

Oncogenic Virome Benefits from the Different Vaginal Microbiome-Immune Axes.

The picture of dynamic interaction between oncogenic viruses and the vaginal bacteria-immune host milieu is incomplete. We evaluated the impact of Polyomaviridae, Papillomaviridae, and Herpesviridae oncoviruses on the vaginal Community State Types (CSTs) and host immune response in reproductive-age women. In our cohort, only Polyomaviridae and Papillomaviridae were detected and were associated with changes in the resident bacteria of CST I and IV (p < 0.05). Lactobacillus crispatus increased in CST I while Prevotella timonensis and Sneathia sanguinegens increased in CST IV. Conversely, CST II and III showed an alteration of the immune response, with the decrease of Eotaxin, MCP-1, IL-7, IL-9, and IL-15 (p < 0.05), leading to reduced antiviral efficacy. An efficient viral clearance was observed only in women from CST I, dominated by Lactobacillus crispatus. Our in vivo study begins to address the knowledge gap with respect to the role of vaginal bacteria and immune response in susceptibility to oncoviral infections

Detecção dos simbiontes relacionados no processo de transmissão de Begomovirus por Bemisia tabaci Genn. meam 1 (Hemiptera: Aleyrodidae), em população geograficamente isolada.

A batata (Solanum tuberosum L.) é afetada por mais de 40 espécies de vírus, sendo que as principais pertencem ao gênero Begomovirus, como o Tomato yellow vein streak virus (ToYVSV). O vírus é transmitido por mosca-branca, Bemisia tabaci Genn. MEAM 1, problema sério à cultura de batata. B. tabaci é considerada atualmente o principal vetor de fitovírus, se alimenta no floema da planta, local onde adquire e transmite os patógenos, e como os demais insetos que se alimentam nesse tecido possuem bactérias endógenas denominadas endossimbiontes ou simbiontes. Os simbiontes são divididos em primários ou obrigatórios e secundários ou facultativos. Em mosca-branca, as bactérias Hamiltonella defensa e Ricketsia spp. já foram descritas como simbiontes que interferem na transmissão de begomovírus. Os objetivos deste trabalho foram; i) estudar o processo de transmissão do ToYVSV por B. tabaci MEAM 1 em batata ?Asterix? e ?Agata?; ii) detectar bactérias simbiontes em indivíduos de B. tabaci e o envolvimento destes no processo de transmissão do ToYVSV. Para tal, indivíduos de B tabaci passaram por períodos de acesso a aquisição (PAA) de 24 e 48h em plantas de tomate (S. lycopersicum L.) infectadas com ToYVSV, após este período, as moscas-brancas foram colocadas em plantas de batata ?Agata? e ?Asterix? (indivíduos/planta) e deixadas por períodos de acesso a inoculação (PAI) de 24h ou 48h. O vírus não foi detectado nas plantas de batata utilizadas nos PAI e nem nos indivíduos de B. tabaci utilizados por 24 e 48h nos PAA e PAI, quando avaliados por PCR. As plantas de batata ?Agata? e ?Asterix? utilizadas nos testes de transmissão não apresentaram sintomas característicos do vírus e nem resultados positivos para detecção do vírus por PCR. Também a detecção do simbionte Hamiltonella foi baixa e não foi detectado simbiontes do gênero Ricketsia nos espécimes de B. tabaci da colônia do Instituto Biológico utilizados nos testes de transmissão. Os resultados obtidos neste experimento podem corroborar com os dados de literatura sugerindo a influência dos endossimbiontes na transmissão de Begomovirus, no entanto, mais estudos para entender melhor essa interação planta-insetomicrorganismo se faz necessário

Fractional CO2 laser for genitourinary syndrome of menopause in breast cancer survivors: clinical, immunological, and microbiological aspects

The composition of vaginal microbiome in menopause and cancer survivor women changes dramatically leading to genitourinary syndrome of menopause (GSM) in up to 70% of patients. Recent reports suggest that laser therapy may be valuable as a not hormonal therapeutic modality. The aim of the present study was to evaluate the effects of fractional CO2 laser treatment on the vaginal secretory pathway of a large panel of immune mediators, usually implicated in tissue remodeling and inflammation, and on microbiome composition in postmenopausal breast cancer survivors. The Ion Torrent PGM platform and the Luminex Bio-Plex platform were used for microbiome and immune factor analysis. The significant reduction of clinical symptoms and the non-significant changes in vaginal microbiome support the efficacy and safety of laser treatment. Moreover, the high remodeling status in vaginal epithelium is demonstrated by the significant changes in inflammatory and modulatory cytokine patterns. Laser therapy can be used for the treatment of GSM symptoms and does not show any adverse effects. However, further studies will be needed to clarify its long-term efficacy and other effects

Liquid biopsy is a promising tool for genetic testing in idiopathic pulmonary fibrosis

Liquid biopsy, which allows the isolation of circulating cell-free (ccf) DNA from blood, is an emerging noninvasive tool widely used in oncology for diagnostic and prognosis purposes. Previous data have shown that serum cfDNA discriminates idiopathic pulmonary fibrosis (IPF) from other interstitial lung diseases. Our study aimed to measure plasma levels of ccfDNA in 59 consecutive therapy-naive and clinically stable IPF patients. The single nucleotide polymorphism (SNP) of the MUC5B gene promoter (rs35705950), associated with increased susceptibility of developing IPF, has been sought in plasma cfDNA and genomic DNA for comparison. Thirty-five age-and sex-matched healthy volunteers were recruited as the control group. Our results show that concentrations of small-size ccfDNA fragments were significantly higher in IPF patients than in controls and inversely correlated with lung function deterioration. Moreover, the median level of 104 ng/mL allowed discriminating patients with mild disease from those more advanced. The rs35705950 polymorphism was found in 11.8% of IPF patients and 8% of controls, with no differences. Complete concordance between ccfDNA and genomic DNA was detected in all control samples, while four out of seven IPF cases (57%) carrying the rs35705950 polymorphism were discordant from genomic DNA (7% of total IPF). Liquid biopsy is a suitable tool with optimistic expectations of application in the field of IPF. In analogy with cancer biology, finding some discrepancies between ccfDNA and genomic DNA in IPF patients suggests that the former may convey specific genetic information present in the primary site of the disease

Potential clinical implications of CD4+CD26high T cells for nivolumab treated melanoma patients

Background Nivolumab is an anti-PD1 antibody that has dramatically improved metastatic melanoma patients’ outcomes. Nevertheless, many patients are resistant to PD-1 inhibition, occasionally experiencing severe of-target immune toxicity. In addition, no robust and reproducible biomarkers have yet been validated to identify the correct selection of patients who will beneft from anti-PD-1 treatment avoiding unwanted side efects. However, the strength of CD26 expression on CD4+ T lymphocytes permits the characterization of three subtypes with variable degrees of responsiveness to tumors, suggesting that the presence of CD26-expressing T cells in patients might be a marker of responsiveness to PD-1-based therapies. Methods The frequency distribution of peripheral blood CD26-expressing cells was investigated employing multiparametric fow cytometry in 69 metastatic melanoma patients along with clinical characteristics and blood count parameters at baseline (W0) and compared to 20 age- and sex-matched healthy controls. Percentages of baseline CD4+CD26high T cells were correlated with the outcome after nivolumab treatment. In addition, the frequency of CD4+CD26high T cells at W0 was compared with those obtained after 12 weeks (W1) of therapy in a sub-cohort of 33 patients. Results Circulating CD4+CD26high T cells were signifcantly reduced in melanoma patients compared to healthy subjects (p=0.001). In addition, a signifcant association was observed between a low baseline percentage of CD4+CD26high T cells (<7.3%) and clinical outcomes, measured as overall survival (p=0.010) and progression-free survival (p=0.014). Moreover, patients with clinical beneft from nivolumab therapy had signifcantly higher frequencies of circulating CD4+CD26high T cells than patients with non-clinical beneft (p=0.004) at 12 months. Also, a higher pre-treatment proportion of circulating CD4+CD26high T cells was correlated with Disease Control Rate (p=0.014) and best Overall Response Rate (p=0.009) at 12 months. Interestingly, after 12 weeks (W1) of nivolumab treatment, percentages of CD4+CD26high T cells were signifcantly higher in comparison with the frequencies measured at W0 (p<0.0001), aligning the cell counts with the ranges seen in the blood of healthy subjects

Levantamento populacional de cigarrinhas, potenciais vetoras de Xylella fastidiosa, sob condições de aumento de dióxido de carbono em plantas de café.

No Brasil, há um complexo de cigarrinhas (Hemiptera: Cicadellidae) associado à cultura do café que transmite a bactéria Xylella fastidiosa e causa a doença conhecida como ?Atrofia dos Ramos do Cafeeiro? (ARC). O experimento no sistema FACE (?Free Air Carbon Dioxide Enrichment?) consistiu de 2 tratamentos, um com aplicação adicional de CO2 (6 anéis com 200 ppmv) e o outro sem aplicação de CO2 (6 anéis). As cigarrinhas foram coletadas quinzenalmente através de uma armadilha adesiva instalada em cada um dos 12 anéis. Algumas cigarrinhas foram selecionadas para extração e amplificação de DNA. Primers específicos para detecção de X. fastidiosa e do simbionte primário - Candidatus Sulcia muelleri - foram utilizados na detecção. Em 2 anos de levantamento foram capturados 9.446 espécimes de cigarrinhas da família Cicadellidae pertencentes a 10 espécies, sendo 4.980 nos anéis com aplicação de CO2 e 4.466 nos anéis sem aplicação de CO2. Observou-se que a porcentagem de cigarrinhas positivas para X. fastidiosa foi extremamente baixa em comparação com a detecção do simbionte. O conhecimento obtido neste trabalho pode ajudar a prever os impactos das mudanças climáticas na biodiversidade de insetos, de patógenos e de simbiontes e auxiliar tanto nas técnicas de manejo integrado de pragas quanto na utilização de espécies indicadoras para efeitos de CO2