Breaking Bad: Inflammasome Activation by Respiratory Viruses.

The nucleotide-binding domain leucine-rich repeat-containing receptor (NLR) family is a group of intracellular sensors activated in response to harmful stimuli, such as invading pathogens. Some NLR family members form large multiprotein complexes known as inflammasomes, acting as a platform for activating the caspase-1-induced canonical inflammatory pathway. The canonical inflammasome pathway triggers the secretion of the pro-inflammatory cytokines interleukin (IL)-1ß and IL-18 by the rapid rupture of the plasma cell membrane, subsequently causing an inflammatory cell death program known as pyroptosis, thereby halting viral replication and removing infected cells. Recent studies have highlighted the importance of inflammasome activation in the response against respiratory viral infections, such as influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While inflammasome activity can contribute to the resolution of respiratory virus infections, dysregulated inflammasome activity can also exacerbate immunopathology, leading to tissue damage and hyperinflammation. In this review, we summarize how different respiratory viruses trigger inflammasome pathways and what harmful effects the inflammasome exerts along with its antiviral immune response during viral infection in the lungs. By understanding the crosstalk between invading pathogens and inflammasome regulation, new therapeutic strategies can be exploited to improve the outcomes of respiratory viral infections.

Pericardite após infarto do miocárdio: o papel da ressonância magnética cardíaca no seu diagnóstico e predição de risco modalidade: imagem cardiovascular multimodalidade / Pericarditis after myocardial infarction: the role of cardiac magnetic resonance in its diagnosis and risk prediction modality: multimodality cardiovascular imaging

RESUMO: A pericardite secundária à injúria miocárdica tornou-se um raro diagnóstico com a propagação do uso da terapia de reperfusão no infarto agudo com supradesnivalemento do segmento ST (IAMCSST). Estudos retrospectivos demonstraram essa complicação em apenas 1,7% dos pacientes com IAMCSST reperfundidos dentro da janela terapêutica. No entanto, ainda são recorrentes os casos de infarto agudo que não são submetidos a terapia em tempo hábil, com possível aumento do risco de pericardite. A ressonância magnética cardíaca (RMC) tem importante papel na avaliação de doenças do pericárdio e na avaliação do território miocárdico infartado. OBJETIVO: Avaliar a prevalência da pericardite em paciente após IAMCSST nãoreperfundidos, avaliados por meio da RMC, e os fatores de risco associados a essa complicação. METODOLOGIA: Estudo retrospectivo transversal com pacientes admitidos em hospital terciário com o diagnóstico de IAMCSST não reperfundidos com mais de 12 horas até 30 dias do início da dor. Todos os pacientes foram submetidos a RMC conforme protocolo institucional, que incluiu sequências ponderadas em T2 para avaliação de edema, e realce tardio com gadolínio objetivando identificação de inflamação no território pericárdico e avaliação da extensão do infarto (figuras 1 e 2). RESULTADOS: Foram avaliados 113 pacientes com IAMCSST não reperfundido, dos quais 13 (11,5%) preenchiam critérios para pericardite aguda pela RMC. Essa incidência foi muito superior à demonstrada naqueles submetidos ao tratamento dentro do tempo recomendado. Parâmetros morfofuncionais que denotam maior acometimento miocárdico pelo infarto, incluindo dilatação das cavidades esquerdas, menor fração de ejeção do ventrículo esquerdo e maior número de seguimentos infartados, demonstraram uma tendência de associação com o diagnóstico da pericardite, apesar da ausência de significância estatística decorrente do pequeno número de casos positivos (Tabela 1). CONCLUSÃO: A RMC é importante método no diagnóstico de pericardite em pacientes com IAMCSST não-reperfundidos. Esse diagnóstico apresentou alta incidência no grupo de pacientes estudado, e estive associado a eventos isquêmicos que resultaram em maior comprometimento morfofuncional do ventrículo esquerdo.

SARS-CoV-2 immune complex triggers human monocyte necroptosis.

We analyzed the ability of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) itself and SARS-CoV-2-IgG immune complexes to trigger human monocyte necroptosis. SARS-CoV-2 was able to induce monocyte necroptosis dependently of MLKL activation. Necroptosis-associated proteins (RIPK1, RIPK3 and MLKL) were involved in SARS-CoV-2N1 gene expression in monocytes. SARS-CoV-2 immune complexes promoted monocyte necroptosis in a RIPK3- and MLKL-dependent manner, and Syk tyrosine kinase was necessary for SARS-CoV-2 immune complex-induced monocyte necroptosis, indicating the involvement of Fcγ receptors on necroptosis. Finally, we provide evidence that elevated LDH levels as a marker of lytic cell death are associated with COVID-19 pathogenesis.

Human Neutrophils Present Mild Activation by Zika Virus But Reduce the Infection of Susceptible Cells.

The emergence of the Zika virus (ZIKV) has highlighted the need for a deeper understanding of virus-host interactions in order to pave the way for the development of antiviral therapies. The present work aimed to address the response of neutrophils during ZIKV infection. Neutrophils are important effector cells in innate immunity implicated in the host's response to neurotropic arboviruses. Our results indicate that human neutrophils were not permissive to Asian or African ZIKV strain replication. In fact, after stimulation with ZIKV, neutrophils were mild primed against the virus as evaluated through CD11b and CD62L modulation, secretion of inflammatory cytokines and granule content, production of reactive oxygen species, and neutrophil extracellular traps formation. Overall, neutrophils did not affect ZIKV infectivity. Moreover, in vitro ZIKV infection of primary innate immune cells did not trigger neutrophil migration. However, neutrophils co-cultured with ZIKV susceptible cell lineages resulted in lower cell infection frequencies, possibly due to cell-to-cell contact. In vivo, neutrophil depletion in immunocompetent mice did not affect ZIKV spreading to the draining lymph nodes. The data suggest that human neutrophils do not play an antiviral role against ZIKV per se, but these cells might participate in an infected environment shaping the ZIKV infection in other target cells.

Insights Into the Role of the Lung Virome During Respiratory Viral Infections.

The virome constitutes the viral component of the microbiome and it consists of the genomes of all the viruses that inhabit a particular region of the human body, including those that cause acute, persistent or latent infection, and retroviral elements integrated to host chromosomes. The human virome is composed by eukaryotic viruses, bacteriophages and archaeal viruses. The understanding of the virome composition and role on human health has been delayed by the absence of specific tools and techniques to accurately characterize viruses. However, more recently, advanced methods for viral diagnostics, such as deep sequencing and metagenomics, have allowed a better understanding of the diverse viral species present in the human body. Previous studies have shown that the respiratory virome modulates the host immunity and that, since childhood, the human lung is populated by viruses for whom there is no disease association. Whether these viruses are potentially pathogenic and the reason for their persistence remain elusive. Increased respiratory viral load can cause exacerbation of chronic pulmonary diseases, including COPD, cystic fibrosis, and asthma. Moreover, the presence of resident viral populations may contribute to the pathogenesis of community-acquired respiratory virus infections. In this mini review, I will discuss the recent progress on our understanding of the human lung virome and summarize the up-to-date knowledge on the relationships among community-acquired respiratory viruses, the lung virome and the immune response to better understand disease pathophysiology and the factors that may lead to viral persistence.

Fungal impact on archaeological materials collected at Byers Peninsula Livingston Island, South Shetland Islands, Antarctica.

We identified cultivable fungi present on the surface of five archaeological sealers' artifacts from the beginning of the 19th century collected on Livingston Island, Antarctica. Twenty fungal isolates were recovered and identified using biology molecular methods as taxa of Antarctomyces, Linnemannia, Penicillium, Mortierella, Talaromyces, and Trichoderma. Penicillium was dominant on artifacts stored at 10 and 25 °C. In contrast, Antarctomyces, Linnemania, Mortierella, and Trichoderma occurred only on artifacts stored between 8 °C and 10 °C. Our results showed that the Antarctic artifacts harboured cosmopolitan mesophilic, cold-tolerant, and endemic psychrophilic fungal taxa. The mesophilic fungi might have contaminated the artifacts in situ, during sampling, transport, and/or storage in the laboratory collection or represent dormant but viable form capable to grow on the objects. However, the detection of cold-tolerant and endemic fungi shows that these fungi, when stored between 8 ° and 10 °C, continue growing on the objects, which may supply them with organic nutrients; this may accelerate degradation of artifacts in the collection. Preventive steps should be adopted to avoid further microbial contamination. Sterilised microbiological conditions can be followed during fieldwork and transportation to Brazil. The preventive protocol may represent a better alternative to avoid artifact microbial proliferation to preserve rare Antarctic archaeological heritage.

Serine proteases in neutrophil extracellular traps exhibit anti-Respiratory Syncytial Virus activity.

Human respiratory syncytial virus (hRSV) is an infectious agent in infants and young children which there are no vaccines or drugs for treatment. Neutrophils are recruited for airway, where they are stimulated by hRSV to release large amounts of neutrophil extracellular traps (NETs). NETs are compound by DNA and proteins, including microbicidal enzymes. They constitute a large part of the mucus accumulated in the lung of patients, compromising their breathing capacity. In contrast, NETs can capture/inactivate hRSV, but the molecules responsible for this effect are unknown. OBJECTIVES: We selected microbicidal NET enzymes (elastase, myeloperoxidase, cathepsin-G, and proteinase-3) to assess their anti-hRSV role. METHODS AND RESULTS: Through in vitro assays using HEp-2 cells, we observed that elastase, proteinase-3, and cathepsin-G, but not myeloperoxidase, showed virucidal effects even at non-cytotoxic concentrations. Elastase and proteinase-3, but not cathepsin-G, cleaved viral F-protein, which is responsible for viral adhesion and fusion with the target cells. Molecular docking analysis indicated the interaction of these macromolecules in the antigenic regions of F-protein through the active regions of the enzymes. CONCLUSIONS: Serine proteases from NETs interact and inactive hRSV. These results contribute to the understanding the role of NETs in hRSV infection and to designing treatment strategies for the inflammatory process during respiratory infections.

Alveolar-like Macrophages Attenuate Respiratory Syncytial Virus Infection.

Respiratory Syncytial Virus (RSV) is the leading cause of acute lower respiratory infections in young children and infection has been linked to the development of persistent lung disease in the form of wheezing and asthma. Despite substantial research efforts, there are no RSV vaccines currently available and an effective monoclonal antibody targeting the RSV fusion protein (palivizumab) is of limited general use given the associated expense. Therefore, the development of novel approaches to prevent RSV infection is highly desirable to improve pediatric health globally. We have developed a method to generate alveolar-like macrophages (ALMs) from pluripotent stem cells. These ALMs have shown potential to promote airway innate immunity and tissue repair and so we hypothesized that ALMs could be used as a strategy to prevent RSV infection. Here, we demonstrate that ALMs are not productively infected by RSV and prevent the infection of epithelial cells. Prevention of epithelial infection was mediated by two different mechanisms: phagocytosis of RSV particles and release of an antiviral soluble factor different from type I interferon. Furthermore, intratracheal administration of ALMs protected mice from subsequent virus-induced weight loss and decreased lung viral titres and inflammation, indicating that ALMs can impair the pathogenesis of RSV infection. Our results support a prophylactic role for ALMs in the setting of RSV infection and warrant further studies on stem cell-derived ALMs as a novel cell-based therapy for pulmonary viral infections.

New Insights on the Early Interaction Between Typhoid and Non-typhoid Salmonella Serovars and the Host Cells.

Salmonella enterica is a common source of food and water-borne infections, causing a wide range of clinical ailments in both human and animal hosts. Immunity to Salmonella involves an interplay between different immune responses, which are rapidly initiated to control bacterial burden. However, Salmonella has developed several strategies to evade and modulate the host immune responses. In this sense, the main knowledge about the pathogenicity of this bacterium has been obtained by the study of mouse models with non-typhoidal serovars. However, this knowledge is not representative of all the pathologies caused by non-typhoidal serovars in the human. Here we review the most important features of typhoidal and non-typhoidal serovars and the diseases they cause in the human host, describing the virulence mechanisms used by these pathogens that have been identified in different models of infection.

Association between TNF-α and IFN-γ levels and severity of acute viral bronchiolitis.

Acute bronchiolitis caused by the respiratory syncytial virus triggers an inflammatory response with the production and release of several pro-inflammatory cytokines. Evidence suggests that their levels are associated with the severity of the infection. This systematic review and meta-analysis aim to assess whether the levels of TNF-α and IFN-γ are associated with the severity of acute viral bronchiolitis. We searched MEDLINE libraries (via PUBMED), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Scientific Electronic Library Online (SciELO), Latin American Caribbean Health Sciences Literature (LILACS), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and the gray literature through April 2020. Random effect models were used for general and subgroup analysis. In total, six studies were included with a total of 744 participants. The mean TNF-α levels between the severe group did not differ from the control group 0.14 (95% CI: -0.53 to 0.82, I2 = 91%, p < 0.01); the heterogeneity was high. The results remained insignificant when the analyses were performed including only studies with high quality 0.25 (95% CI: -0.46 to 0.96, I2 = 92%, p < 0.01) I2 = 95%, p = 0.815), when TNF-α was nasal 0.60 (95% CI: -0.49 to 1.69), I2 = 94%, p < 0.01), or serum -0.08 (95% CI: -0.48 to 0.31), I2 = 29%, p = 0.24). In the analysis of studies measuring IFN-γ, there was also no significance of -0.67 (95% CI: -1.56 to 0.22, I2 = 76%, p = 0.04). In conclusion, this meta-analysis suggests that the most severe patients do not have different mean TNF-α and IFN-γ values ​than patients with mild disease, but the heterogeneity of the studies was high. Supplemental data for this article is available online at https://doi.org/10.1080/08830185.2021.1889534.

The triad: respiratory microbiome - virus - immune response in the pathophysiology of pulmonary viral infections.

INTRODUCTION: The longstanding dogma that the healthy lung is sterile has been refuted by recent advances in culture-independent analyses of airway samples. The respiratory microbiome comprises all airway and lung tissue-associated microbes. These micro-organisms occur throughout the upper and lower respiratory tracts, with different populations and distinct burdens at specific sites and can be classified as pathogenic or commensal. AREAS COVERED: The majority of studies investigating the respiratory microbiome have focused on bacteria; however, emerging evidence has revealed the composition of the lung virome, the global viral communities present in the lung tissue. In this review, we searched PubMed and used keywords such as airway microbiome. We restricted outputs to English language and did not limit by any dates. We summarize the up-to-date knowledge on how the microbiome interacts with the host immune system and influences the pathogenesis of pulmonary viral infections. EXPERT OPINION: The relationship between colonizing microbes and the host is complex and various factors need to be considered in order to appreciate its pathophysiological consequences. Understanding these intricate mechanisms of interaction among the respiratory microbiome, viruses and the immune response may lead to the development of better therapies to treat or prevent respiratory viral infections.

TNF-mediated alveolar macrophage necroptosis drives disease pathogenesis during respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is the major cause of acute bronchiolitis in infants under 2 years old. Necroptosis has been implicated in the outcomes of respiratory virus infections. We report that RSV infection triggers necroptosis in primary mouse macrophages and human monocytes in a RIPK1-, RIPK3- and MLKL-dependent manner. Moreover, necroptosis pathways are harmful to RSV clearance from alveolar macrophages. Additionally, Ripk3-/- mice were protected from RSV-induced weight loss and presented with reduced viral loads in the lungs.Alveolar macrophage depletion also protected mice from weight loss and decreased lung RSV virus load. Importantly, alveolar macrophage depletion abolished the upregulation of Ripk3 and Mlkl gene expression induced by RSV infection in the lung tissue.Autocrine tumor necrosis factor (TNF)-mediated RSV-triggered macrophage necroptosis and necroptosis pathways were also involved in TNF secretion even when macrophages were committed to cell death, which can worsen lung injury during RSV infection. In line, Tnfr1-/- mice had a marked decrease in Ripk3 and Mlkl gene expression and a sharp reduction in the numbers of necrotic alveolar macrophages in the lungs. Finally, we provide evidence that elevated nasal levels of TNF are associated with disease severity in infants with RSV bronchiolitis.We propose that targeting TNF and/or the necroptotic machinery may be valuable therapeutic approaches to reduce the respiratory morbidity caused by RSV infection in young children.

Diversity and distribution of cultivable fungi present in acid sulphate soils in chronosequence under para-periglacial conditions in King George Island, Antarctica.

We recovered 85 fungal isolates from the acid sulphate soils in chronosequence under para-periglacial conditions in King George Island, Antarctica. Thirty-two taxa belonging to the phylum Ascomycota, Basidiomycota and Mortierellomycota were identified. Mortierella amoeboidea, Mortierella sp. 2, Mortierella sp. 3, Penicillium sp. 2 and Penicillium sp. 3 dominated the sulphite soils. Despite the multi-extreme physic-chemical conditions of the sulphate soils (low pH, variable content of macro and micronutrients and organic matter), the fungal assemblages exhibited moderate diversity indices, which ranged according to the degree of soil development. Soils with more weathered and, consequently, with highest values of organic carbon shelter the most diverse fungal assemblages, which can be associated with the occurrence of sulphurisation and sulphide oxidation. Different taxa of Mortierella and Penicillium displayed broad pH (3-9) and temperature (5-35 °C) plasticity. The multi-extreme sulphite soils of Antarctica revealed the presence of moderate fungal diversity comprising cold cosmopolitan and psychrophilic endemic taxa. Among these, Mortierella and Penicillium, known to survive in extreme conditions such as low temperature and available organic matter, low pH and high concentrations of metals, might represent interesting techniques to be used in biotechnological processes such as bioleaching in metallurgy and phosphate solubilisation in agriculture.

The role of extracellular nucleic acids in the immune system modulation of Rhodnius prolixus (Hemiptera: Reduviidae).

Extracellular traps (ETs) are extracellular nucleic acids associated with cytoplasmic proteins that may aid in the capture and killing of pathogens. To date, only a few insects were shown to display this kind of immune response. Jaburetox, a peptide derived from jack bean urease, showed toxic effects in Rhodnius prolixus, affecting its immune response. The present study aims to evaluate the role of extracellular nucleic acids in R. prolixus' immune response, using Jaburetox as a model entomotoxin. The insects were treated with extracellular nucleic acids and/or Jaburetox, and the cellular and humoral responses were assessed. We also evaluated the release of extracellular nucleic acids induced by toxins, and performed immunocompetence assays using pathogenic bacteria. Our results demonstrated that extracellular nucleic acids can modulate the insect immune responses, either alone or associated with the toxin. Although RNA and DNA induced a cellular immune response, only DNA was able to neutralize the Jaburetox-induced aggregation of hemocytes. Likewise, the activation of the humoral response was different for RNA and DNA. Nevertheless, it was observed that both, extracellular DNA and RNA, immunocompensated the Jaburetox effects on insect defenses upon the challenge of a pathogenic bacterium. The toxin was not able to alter cellular viability, in spite of inducing an increase in the reactive species of oxygen formation. In conclusion, we have demonstrated a protective role for extracellular nucleic acids in R. prolixus´ immune response to toxins and pathogenic bacteria.

Fungi in glacial ice of Antarctica: diversity, distribution and bioprospecting of bioactive compounds.

We identified cultivable fungi present in the glacial ice fragments collected in nine sites across Antarctica Peninsula and assessed their abilities to produce bioactive compounds. Three ice fragments with approximately 20 kg were collected, melted and 3 L filtered through of 0.45 µm sterilized membranes, which were placed on the media Sabouraud agar and minimal medium incubated at 10 °C. We collected 66 isolates classified into 27 taxa of 14 genera. Penicillium palitans, Penicillium sp. 1, Thelebolus balaustiformis, Glaciozyma antarctica, Penicillium sp. 7, Rhodotorula mucilaginosa, and Rhodotorula dairenensis had the highest frequencies. The diversity and richness of the fungal community were high with moderate dominance. Penicillium species were present in all samples, with Penicillium chrysogenum showing the broadest distribution. P. chrysogenum, P. palitans, and Penicillium spp. had trypanocidal, leishmanicidal, and herbicidal activities, with P. chrysogenum having the broadest and highest capability. 1H NMR signals revealed the presence of highly functionalized secondary metabolites in the bioactive extracts. Despite extreme environmental conditions, glacial ice harbours a diverse fungal community, including species never before recorded in the Arctic and Antarctica. Among them, Penicillium taxa may represent wild fungal strains with genetic and biochemical pathways that may produce new secondary bioactive metabolites.

Treatment with selenium-enriched Saccharomyces cerevisiae UFMG A-905 partially ameliorates mucositis induced by 5-fluorouracil in mice.

PURPOSE: Gastrointestinal mucositis is a major problem associated with cancer therapy. To minimize these deleterious effects, simultaneous administration of antioxidant components, such as selenium, can be considered. There is a growing interest in the use of yeasts because they are able to convert inorganic selenium into selenomethionine. In the present study, oral administration of Saccharomyces cerevisiae UFMG A-905 enriched with selenium was evaluated as an alternative in minimizing the side effects of 5FU-induced mucositis in mice. METHODS: Mice body weight, food consumption, faeces consistency and the presence of blood in faeces were assessed daily during experimental mucositis induced by 5-fluorouracil (5FU). Blood was used for intestinal permeability determination, and small intestine for oxidative stress, immunological and histopathological examination. RESULTS: The increased intestinal permeability observed with mucositis induction was partially reverted by S. cerevisiae and selenium-enriched yeast. Both treatments were able to reduce myeloperoxidase activity, but only selenium-enriched yeast reduced eosinophil peroxidase activity. CXCL1/KC levels, histopathological tissue damage and oxidative stress (lipid peroxidation and nitrite production) in the small intestine were reduced by both treatments; however, this reduction was always higher when treatment with selenium-enriched yeast was evaluated. CONCLUSIONS: Results of the present study showed that the oral administration of S. cerevisiae UFMG A-905 protected mice against mucositis induced by 5-FU, and that this effect was potentiated when the yeast was enriched with selenium.

Macrophage migration inhibitory factor (MIF) controls cytokine release during respiratory syncytial virus infection in macrophages.

OBJECTIVE AND DESIGN: Respiratory syncytial virus (RSV) is the major cause of infection in children up to 2 years old and reinfection is very common among patients. Tissue damage in the lung caused by RSV leads to an immune response and infected cells activate multiple signaling pathways and massive production of inflammatory mediators like macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine. Therefore, we sought to investigate the role of MIF during RSV infection in macrophages. METHODS: We evaluated MIF expression in BALB/c mice-derived macrophages stimulated with different concentrations of RSV by Western blot and real-time PCR. Additionally, different inhibitors of signaling pathways and ROS were used to evaluate their importance for MIF expression. Furthermore, we used a specific MIF inhibitor, ISO-1, to evaluate the role of MIF in viral clearance and in RSV-induced TNF-α, MCP-1 and IL-10 release from macrophages. RESULTS: We showed that RSV induces MIF expression dependently of ROS, 5-LOX, COX and PI3K activation. Moreover, viral replication is necessary for RSV-triggered MIF expression. Differently, p38 MAPK in only partially needed for RSV-induced MIF expression. In addition, MIF is important for the release of TNF-α, MCP-1 and IL-10 triggered by RSV in macrophages. CONCLUSIONS: In conclusion, we demonstrate that MIF is expressed during RSV infection and controls the release of pro-inflammatory cytokines from macrophages in an in vitro model.

Evaluation of nasal levels of interferon and clinical severity of influenza in children.

BACKGROUND: Experimental data show that type I interferon has a key role in innate immune response against influenza infection. OBJECTIVE: We compared nasal levels of interferon-α2 and ß among inpatients and outpatients with influenza. STUDY DESIGN: Children younger than 5 years of age with influenza-like illness seeking care at the emergency department within the first 72 h of disease onset were prospectively included. Clinical and demographic data and secretions through nasal wash were obtained. Influenza infection was assessed through reverse-transcription polymerase chain reaction and nasal levels of interferon-α2 and ß were measured by enzyme-linked immunosorbent assay. All patients followed until the end of the disease. RESULTS: One hundred patients were included, of which 24 had confirmed influenza infection, and 5 of them were hospitalized. Subtypes A (H3N2) and B were confirmed in 10 and 14 patients, respectively. Seventy-six patients without influenza, including 48% of outpatients, were recruited as controls. All hospitalized patients were significantly younger regardless of influenza status (age <6 months in 59% vs. 23.2%, p < 0.001). All other data were similar among the groups. Comparing median levels of interferon-α2 among children with influenza, levels were significantly higher in outpatients than in hospitalized patients and were 263.2 pg/mL (25-75 interquartile range: 58.3-634) and detectable in only one patient (90 pg/mL), respectively. The levels of interferon-α2 in controls and those of interferon-ß in all groups were not detected. CONCLUSIONS: Higher levels of interferon-α2 in patients with less severe influenza reinforce experimental evidence about the protective role of interferon-α2 against influenza infection.