Viral Infection Modulates Airway Epithelial Responsiveness To Subsequent Bacterial Infection

Abstract Background Readily-available diagnostics do not reliably discriminate between viral and bacterial pediatric uncomplicated pneumonia, both of which are common. Some have suggested that assessment of pneumococcal carriage could be used to identify those children with bacterial pneumonia. The objective of this study was to determine if nasopharyngeal pneumococcal colonization patterns differed between children with definite viral disease, definite bacterial disease, and respiratory disease of indeterminate etiology. Methods Three groups of subjects were recruited: children with critical respiratory illness, previously healthy children with respiratory illness admitted to the ward, and previously healthy children diagnosed in the emergency department with non-severe pneumonia. Subjects were categorized as follows: a) viral infection syndrome (eg. bronchiolitis), b) bacterial infection syndrome (ie. pneumonia complicated by effusion/empyema), or c) ‘indeterminate’ pneumonia. Subjects’ nasopharyngeal swabs underwent quantitative PCR testing for S. pneumoniae. Associations between categorical variables were determined with Fisher’s exact, chi-square, or logistic regression, as appropriate. Associations between quantitative genomic load and categorical variables was determined by linear regression. Results There were 206 children in Group 1, 122 children in Group 2, and 179 children in Group 3. Only a minority (227/507, 45%) had detectable pneumococcal carriage; in those subjects, there was no association of quantitative genomic load with age, recruitment group, or disease category. In multivariate logistic regression, pneumococcal colonization > 3 log copies/mL was associated with younger age and recruitment group, but not with disease category. Conclusions The nasopharyngeal S. pneumoniae colonization patterns of subjects with definite viral infection were very similar to colonization patterns of those with definite bacterial infection or indeterminate pneumonia. Assessment and quantification of nasopharyngeal pneumococcal colonization does not therefore appear useful to discriminate between acute viral and bacterial respiratory disease; consequently, this diagnostic testing is unlikely to reliably determine which children with indeterminate pneumonia have a bacterial etiology and/or require antibiotic treatment.

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The host transcriptional response to Candidemia is dominated by neutrophil activation and heme biosynthesis and supports novel diagnostic approaches

Genome Medicine ◽

10.1186/s13073-021-00924-9 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Julie M. Steinbrink ◽

Rachel A. Myers ◽

Kaiyuan Hua ◽

Melissa D. Johnson ◽

Jessica L. Seidelman ◽

...

Keyword(s):

Immune Response ◽

Bacterial Infection ◽

Viral Infection ◽

Fungal Infection ◽

Host Response ◽

Hospitalized Patients ◽

Neutrophil Activation ◽

Heme Biosynthesis ◽

Transcriptional Analysis ◽

Diagnostic Approaches

Abstract Background Candidemia is one of the most common nosocomial bloodstream infections in the United States, causing significant morbidity and mortality in hospitalized patients, but the breadth of the host response to Candida infections in human patients remains poorly defined. Methods In order to better define the host response to Candida infection at the transcriptional level, we performed RNA sequencing on serial peripheral blood samples from 48 hospitalized patients with blood cultures positive for Candida species and compared them to patients with other acute viral, bacterial, and non-infectious illnesses. Regularized multinomial regression was utilized to develop pathogen class-specific gene expression classifiers. Results Candidemia triggers a unique, robust, and conserved transcriptomic response in human hosts with 1641 genes differentially upregulated compared to healthy controls. Many of these genes corresponded to components of the immune response to fungal infection, heavily weighted toward neutrophil activation, heme biosynthesis, and T cell signaling. We developed pathogen class-specific classifiers from these unique signals capable of identifying and differentiating candidemia, viral, or bacterial infection across a variety of hosts with a high degree of accuracy (auROC 0.98 for candidemia, 0.99 for viral and bacterial infection). This classifier was validated on two separate human cohorts (auROC 0.88 for viral infection and 0.87 for bacterial infection in one cohort; auROC 0.97 in another cohort) and an in vitro model (auROC 0.94 for fungal infection, 0.96 for bacterial, and 0.90 for viral infection). Conclusions Transcriptional analysis of circulating leukocytes in patients with acute Candida infections defines novel aspects of the breadth of the human immune response during candidemia and suggests promising diagnostic approaches for simultaneously differentiating multiple types of clinical illnesses in at-risk, acutely ill patients.

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CF Monocyte Derived Macrophages Have an Attenuated Response to Extracellular Vesicles Secreted by Airway Epithelial Cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00621.2020 ◽

2021 ◽

Author(s):

Katja Koeppen ◽

Amanda B Nymon ◽

Roxanna Barnaby ◽

Zhongyou Li ◽

Thomas H Hampton ◽

...

Keyword(s):

Immune Response ◽

Epithelial Cells ◽

Bacterial Infection ◽

Extracellular Vesicles ◽

Cell Types ◽

Airway Epithelial Cells ◽

Innate Immune ◽

Airway Epithelial ◽

Immune Genes ◽

Innate Immune Genes

Mutations in CFTR alter macrophage responses, for example, by reducing their ability to phagocytose and kill bacteria. Altered macrophage responses may facilitate bacterial infection and inflammation in the lungs, contributing to morbidity and mortality in cystic fibrosis (CF). Extracellular vesicles (EVs) are secreted by multiple cell types in the lungs and participate in the host immune response to bacterial infection, but the effect of EVs secreted by CF airway epithelial cells (AEC) on CF macrophages is unknown. This report examines the effect of EVs secreted by primary AEC on monocyte derived macrophages (MDM) and contrasts responses of CF and WT MDM. We found that EVs generally increase pro-inflammatory cytokine secretion and expression of innate immune genes in MDM, especially when EVs are derived from AEC exposed to Pseudomonas aeruginosa, and that this effect is attenuated in CF MDM. Specifically, EVs secreted by P. aeruginosa exposed AEC induced immune response genes and increased secretion of pro-inflammatory cytokines, chemoattractants and chemokines involved in tissue repair by WT MDM, but these effects were less robust in CF MDM. We attribute attenuated responses by CF MDM to differences between CF and WT macrophages because EVs secreted by CF AEC or WT AEC elicited similar responses in CF MDM. Our findings demonstrate the importance of AEC EVs in macrophage responses and show that the Phe508del mutation in CFTR attenuates the innate immune response of MDM to EVs.

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Serum procalcitonin measurement for the detection of bacterial infection vs disease flare and viral infection in sle patients

Clinica Chimica Acta ◽

10.1016/j.cca.2019.03.221 ◽

2019 ◽

Vol 493 ◽

pp. S104

Author(s):

N.F. Ahmad Zabidi ◽

T.M. Thevarajah

Keyword(s):

Bacterial Infection ◽

Viral Infection ◽

Disease Flare

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EGFR activation suppresses respiratory virus-induced IRF1-dependent CXCL10 production

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00368.2013 ◽

2014 ◽

Vol 307 (2) ◽

pp. L186-L196 ◽

Cited By ~ 27

Author(s):

April Kalinowski ◽

Iris Ueki ◽

Gundula Min-Oo ◽

Eric Ballon-Landa ◽

David Knoff ◽

...

Keyword(s):

Epithelial Cells ◽

Viral Infection ◽

Airway Epithelium ◽

Respiratory Virus ◽

Respiratory Viruses ◽

Airway Epithelial Cells ◽

Airway Epithelial ◽

Egfr Signaling ◽

Respiratory Viral Infection ◽

Egfr Activation

Airway epithelial cells are the primary cell type involved in respiratory viral infection. Upon infection, airway epithelium plays a critical role in host defense against viral infection by contributing to innate and adaptive immune responses. Influenza A virus, rhinovirus, and respiratory syncytial virus (RSV) represent a broad range of human viral pathogens that cause viral pneumonia and induce exacerbations of asthma and chronic obstructive pulmonary disease. These respiratory viruses induce airway epithelial production of IL-8, which involves epidermal growth factor receptor (EGFR) activation. EGFR activation involves an integrated signaling pathway that includes NADPH oxidase activation of metalloproteinase, and EGFR proligand release that activates EGFR. Because respiratory viruses have been shown to activate EGFR via this signaling pathway in airway epithelium, we investigated the effect of virus-induced EGFR activation on airway epithelial antiviral responses. CXCL10, a chemokine produced by airway epithelial cells in response to respiratory viral infection, contributes to the recruitment of lymphocytes to target and kill virus-infected cells. While respiratory viruses activate EGFR, the interaction between CXCL10 and EGFR signaling pathways is unclear, and the potential for EGFR signaling to suppress CXCL10 has not been explored. Here, we report that respiratory virus-induced EGFR activation suppresses CXCL10 production. We found that influenza virus-, rhinovirus-, and RSV-induced EGFR activation suppressed IFN regulatory factor (IRF) 1-dependent CXCL10 production. In addition, inhibition of EGFR during viral infection augmented IRF1 and CXCL10. These findings describe a novel mechanism that viruses use to suppress endogenous antiviral defenses, and provide potential targets for future therapies.

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Pattern of Cutaneous Dermatoses in Type 2 Diabetes Mellitus in a Tertiary Hospital: A Cross Sectional Study

TAJ Journal of Teachers Association ◽

10.3329/taj.v31i1.41569 ◽

2019 ◽

Vol 31 (1) ◽

pp. 21-28

Author(s):

Mahfuza Akhter ◽

Ishrat Bhuiyan ◽

Zubaida Akter ◽

Homayra Tahseen Hossain ◽

Syed Ghulam Mogni Mowla

Keyword(s):

Diabetes Mellitus ◽

Bacterial Infection ◽

Viral Infection ◽

Fungal Infection ◽

Parasitic Infection ◽

Parasitic Infections ◽

Diabetic Patients ◽

Cutaneous Manifestations ◽

Female Patients

Background: Diabetes mellitus (DM) continues to be a major public health problem. Multiple factors have a role in the skin manifestations of DM. Cutaneous manifestations of DM are very important to the clinician. Methods: Current study was carried out in the Department of Dermatology and Venereology, Shaheed Suhrawrdy Medical College Hospital, Dhaka, spanning from 1st January 2017 till 30th June 2017 over a period of six months. Adult patients already diagnosed to be suffering from type 2 DM presenting with cutaneous manifestations were included in the study. Results: Majority (68.0%) patients had diabetes >5 years, 16.7% had < 1 year and 15.3% had 1-5 years. Family history of DM was found in 70.7% in this study. In this study bacterial infection and fungal infection were more common in female patients (60.0% vs 62.0% respectively). Regarding types of dermatoses, fungal infection was more common in this study 50(33.3%). Others were bacterial infection 20(13.3%), viral infection 7(4.7%) and parasitic infection 7(4.7%). Papulo squamous disease was found 31(20.7%) patients, other diseases were 32(21.3%).Viral infection was more in male patients (71.4%). Parasitic infection was high in female patients 6(85.7%). Papulo squamous diseases was found 21(67.7%) in female patients. Conclusion: In this study fungal infection, bacterial infection, viral infection and parasitic infections were found to be the more common cutaneous dermatoses among adult diabetic patients. Bacterial infection and fungal infection were more common in female patients. TAJ 2018; 31(1): 21-28

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Virus Infection-Induced Bronchial Asthma Exacerbation

Pulmonary Medicine ◽

10.1155/2012/834826 ◽

2012 ◽

Vol 2012 ◽

pp. 1-14 ◽

Cited By ~ 26

Author(s):

Mutsuo Yamaya

Keyword(s):

Epithelial Cells ◽

Viral Infection ◽

Airway Inflammation ◽

Bronchial Asthma ◽

Inflammatory Mediators ◽

Asthma Exacerbation ◽

Viral Infections ◽

Inflammatory Cells ◽

Airway Epithelial Cells ◽

Airway Epithelial

Infection with respiratory viruses, including rhinoviruses, influenza virus, and respiratory syncytial virus, exacerbates asthma, which is associated with processes such as airway inflammation, airway hyperresponsiveness, and mucus hypersecretion. In patients with viral infections and with infection-induced asthma exacerbation, inflammatory mediators and substances, including interleukins (ILs), leukotrienes and histamine, have been identified in the airway secretions, serum, plasma, and urine. Viral infections induce an accumulation of inflammatory cells in the airway mucosa and submucosa, including neutrophils, lymphocytes and eosinophils. Viral infections also enhance the production of inflammatory mediators and substances in airway epithelial cells, mast cells, and other inflammatory cells, such as IL-1, IL-6, IL-8, GM-CSF, RANTES, histamine, and intercellular adhesion molecule-1. Viral infections affect the barrier function of the airway epithelial cells and vascular endothelial cells. Recent reports have demonstrated augmented viral production mediated by an impaired interferon response in the airway epithelial cells of asthma patients. Several drugs used for the treatment of bronchial asthma reduce viral and pro-inflammatory cytokine release from airway epithelial cells infected with viruses. Here, I review the literature on the pathogenesis of the viral infection-induced exacerbation of asthma and on the modulation of viral infection-induced airway inflammation.

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Exposure to common respiratory bacteria alters the airway epithelial response to subsequent viral infection

Respiratory Research ◽

10.1186/s12931-016-0382-z ◽

2016 ◽

Vol 17 (1) ◽

Cited By ~ 26

Author(s):

Carla Bellinghausen ◽

Fahad Gulraiz ◽

Alexandra C. A. Heinzmann ◽

Mieke A. Dentener ◽

Paul H. M. Savelkoul ◽

...

Keyword(s):

Viral Infection ◽

Airway Epithelial

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Study of the role of an infectious factor in the development of stroke in children. Results of a 5-year retrospective analysis

CHILDREN INFECTIONS ◽

10.22627/2072-8107-2021-20-2-10-15 ◽

2021 ◽

Vol 20 (2) ◽

pp. 10-15

Author(s):

A. A. Ivanova ◽

O. V. Shamsheva ◽

I. O. Shchederkina

Keyword(s):

Bacterial Infection ◽

Viral Infection ◽

Retrospective Analysis ◽

Bacterial Infections ◽

Sinus Thrombosis ◽

Risk Groups ◽

Additional Risk Factor ◽

Additional Risk ◽

One Year

Objective: Determine the role of infectious diseases in the development of strokes in children and to identify risk groups for its progression.Materials and Methods: A retrospective analysis of 660 case histories of children aged 1 months to 1 8 years old, hospitalized in Morozov Children's City Clinical Hospital with stroke in the period from 201 6 to July 2020 was carried out.Results. An infectious disease or fever 4 weeks before stroke is diagnosed in 78 (1 2%) cases. Infections more often act as a stroke trigger in children under 7 years old (28% in children under one year old). The incidence of strokes against a background of a bacterial infection is higher than against a background of a viral infection (47% versus 35%). Among bacterial infections, meningitis (35%), otitis media (24%), pneumonia (1 8%) prevailed. With a viral infection, viruses of Herpes are more common (44%), as well as respiratory viruses (37%). Two cases of cerebrovascular accident were revealed in children who have undergone a new coro-navirus infection SARS-CoV-2 (7%). Among the types of stroke, with bacterial infection, sinus thrombosis was more common (50%), among viral infection, the most common was ischemic stroke (60%). The presence of an additional risk factor was revealed in 72%, most often these were prothrombotic conditions (35%).

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