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Immunopathology of viral pneumonia

Karen Bohmwald, Janyra A Espinoza, Raúl A Pulgar, Evelyn L Jara, Alexis M Kalergis
The mononuclear phagocyte system (MPS) comprises of monocytes, macrophages (MΦ), and dendritic cells (DCs). MPS is part of the first line of immune defense against a wide range of pathogens, including viruses, such as the human respiratory syncytial virus (hRSV). The hRSV is an enveloped virus that belongs to the Pneumoviridae family, Orthopneumovirus genus. This virus is the main etiological agent causing severe acute lower respiratory tract infection, especially in infants, children and the elderly. Human RSV can cause bronchiolitis and pneumonia and it has also been implicated in the development of recurrent wheezing and asthma...
2017: Frontiers in Immunology
Alireza Tahamtan, Yazdan Samieipoor, Fatemeh Sadat Nayeri, Ali Akbar Rahbarimanesh, Anahita Izadi, Ali Rashidi-Nezhad, Masoumeh Tavakoli-Yaraki, Mohammad Farahmand, Louis Bont, Fazel Shokri, Talat Mokhatri-Azad, Vahid Salimi
An accumulating body of evidence suggests that the endocannabinoid system plays a significant role in pathophysiological processes and impacts disease severity. Here we investigate the possible role of a cannabinoid receptor type 2 (CB2) functional variant in determining disease severity and the potential pharmacological therapeutic effects of CB2 activation in viral respiratory infection. The common missense variant (CAA/CGG; Q63R) of the gene-encoding CB2 receptor (CNR2) was evaluated in 90 inpatient and 90 outpatient children with acute respiratory tract infection (ARTI)...
January 1, 2018: Virulence
Lana Vandersarren, Cedric Bosteels, Manon Vanheerswynghels, James J Moon, Andrew J Easton, Gert Van Isterdael, Sophie Janssens, Bart N Lambrecht, Mary J van Helden
Pneumonia virus of mice (PVM) infection has been widely used as a rodent model to study the closely related human respiratory syncytial virus (hRSV). While T cells are indispensable for viral clearance, they also contribute to immunopathology. To gain more insight into mechanistic details, novel tools are needed that allow to study virus-specific T cells in C57BL/6 mice as the majority of transgenic mice are only available on this background. While PVM-specific CD8 T cell epitopes were recently described, so far no PVM-specific CD4 T cell epitopes have been identified within the C57BL/6 strain...
June 14, 2017: Scientific Reports
Malgorzata Pawełczyk, Marek Leszek Kowalski
Viral infections are leading causes of both upper and lower airway acute illness in all age groups of healthy persons, and have also been implicated in the acute exacerbations of chronic respiratory disorders like asthma and COPD. Human rhinovirus, respiratory syncytial virus, influenza virus and coronavirus have been considered as the most important respiratory pathogens and relatively little attention has been paid to the role of parainfluenza viruses (hPIVs). Human parainfluenza viruses are single-stranded RNA viruses belonging to the paramyxovirus family that may evoke lower respiratory infections in infants, children and immunocompromised individuals...
March 2017: Current Allergy and Asthma Reports
Kristin M Wiese, Bria M Coates, Karen M Ridge
Pneumonia is caused by both viral and bacterial pathogens and is responsible for a significant health burden in the Unites States. The innate immune system is the human body's first line of defense against these pathogens. The recognition of invading pathogens via pattern recognition receptors leads to proinflammatory cytokine and chemokine production, followed by recruitment and activation of effector immune cells. The nonspecific inflammatory nature of the innate immune response can result in immunopathology that is detrimental to the host...
August 2017: American Journal of Respiratory Cell and Molecular Biology
Jonathan Hoffmann, Daniela Machado, Olivier Terrier, Stephane Pouzol, Mélina Messaoudi, Wilma Basualdo, Emilio E Espínola, Rosa M Guillen, Manuel Rosa-Calatrava, Valentina Picot, Thomas Bénet, Hubert Endtz, Graciela Russomando, Gláucia Paranhos-Baccalà
Mixed viral and bacterial infections are widely described in community-acquired pneumonia; however, the clinical implications of co-infection on the associated immunopathology remain poorly studied. In this study, microRNA, mRNA and cytokine/chemokine secretion profiling were investigated for human monocyte-derived macrophages infected in-vitro with Influenza virus A/H1N1 and/or Streptococcus pneumoniae. We observed that the in-vitro co-infection synergistically increased interferon-γ-induced protein-10 (CXCL10, IP-10) expression compared to the singly-infected cells conditions...
December 6, 2016: Scientific Reports
Rudragouda Channappanavar, Anthony R Fehr, Rahul Vijay, Matthias Mack, Jincun Zhao, David K Meyerholz, Stanley Perlman
Highly pathogenic human respiratory coronaviruses cause acute lethal disease characterized by exuberant inflammatory responses and lung damage. However, the factors leading to lung pathology are not well understood. Using mice infected with SARS (severe acute respiratory syndrome)-CoV, we show that robust virus replication accompanied by delayed type I interferon (IFN-I) signaling orchestrates inflammatory responses and lung immunopathology with diminished survival. IFN-I remains detectable until after virus titers peak, but early IFN-I administration ameliorates immunopathology...
February 10, 2016: Cell Host & Microbe
Pali D Shah, Qiong Zhong, Elizabeth A Lendermon, Matthew R Pipeling, John F McDyer
Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in immunocompromised hosts, many of whom undergo significant periods of lymphopenia. However, the impact of lymphopenia and subsequent immune reconstitution on T cell responses and pulmonary pathology are poorly understood. Using a model of primary murine CMV infection in mice treated with cyclophosphamide (CY), the relationship of CD8+ T cell reconstitution to pneumonitis pathology was studied. Female BALB/c mice were infected with murine CMV (MCMV) with/without CY on day 1 post-infection...
June 2015: Viral Immunology
Xuancheng Guo, Taixiang Liu, Hengfei Shi, Jingjing Wang, Ping Ji, Hongwei Wang, Yayi Hou, Ren Xiang Tan, Erguang Li
UNLABELLED: Respiratory syncytial virus (RSV) is the leading cause of acute respiratory tract viral infection in infants, causing bronchiolitis and pneumonia. The host antiviral response to RSV acts via retinoic acid-inducible gene I (RIG-I). We show here that RSV infection upregulates major histocompatibility complex class I (MHC-I) expression through the induction of NLRC5, a NOD-like, CARD domain-containing intracellular protein that has recently been identified as a class I MHC transactivator (CITA)...
August 2015: Journal of Virology
V E Kazmirchuk, V V Tsarik, D V Mal'tsev, M I Ishchenko
Diagnostic criteria of sarcoidosis were offered in the 60-ies of XX century, however today the problem of sarcoidosis is difficult for understanding the different specialists and early detection. The development of laboratory diagnostic of viral infections and introduction of polymerase chain reaction (PCR) has greatly improved the level of diagnosis of herpes infections, reveal the previously unknown etiology of many diseases: sarcoidosis (granulomatosis), migraine, multiple sclerosis, cystic prenatal brain damage, convulsions, Hodgkin's disease and others...
January 2014: Likars'ka Sprava
Hazem E Ghoneim, Jonathan A McCullers
Secondary bacterial pneumonia is a significant cause of morbidity and mortality during influenza, despite routine use of standard antibiotics. Antibiotic-induced immunopathology associated with bacterial cell wall lysis has been suggested to contribute to these poor outcomes. Using Streptococcus pneumoniae in a well-established murine model of secondary bacterial pneumonia (SBP) following influenza, we stratified disease severity based on pneumococcal load in the lungs via in vivo bioluminescence imaging. Ampicillin treatment cured mice with mild pneumonia but was ineffective against severely pneumonic mice, despite effective bacterial killing...
May 1, 2014: Journal of Infectious Diseases
Stefanie Frey, Hanspeter Pircher, Marie Follo, Peter Collins, Christine Krempl, Stephan Ehl
Cytotoxic T cells (CTL) play a critical role in the clearance of respiratory viral infections, but they also contribute to disease manifestations. In this study, we infected mice with a genetically modified pneumonia virus of mice (PVM) that allowed visualization of virus-specific CTL and infected cells in situ. The first virus-specific T cells entered the lung via blood vessels in the scattered foci of PVM-infected cells, which densely clustered around the bronchi at day 7 after infection. At this time, overall pulmonary virus load was maximal, but the mice showed no overt signs of disease...
October 2013: Journal of Virology
Sarah N Lauder, Emma Jones, Kathryn Smart, Anja Bloom, Anwen S Williams, James P Hindley, Beatrice Ondondo, Philip R Taylor, Mathew Clement, Ceri Fielding, Andrew J Godkin, Simon A Jones, Awen M Gallimore
Balancing the generation of immune responses capable of controlling virus replication with those causing immunopathology is critical for the survival of the host and resolution of influenza-induced inflammation. Based on the capacity of interleukin-6 (IL-6) to govern both optimal T-cell responses and inflammatory resolution, we hypothesised that IL-6 plays an important role in maintaining this balance. Comparison of innate and adaptive immune responses in influenza-infected wild-type control and IL-6-deficient mice revealed striking differences in virus clearance, lung immunopathology and generation of heterosubtypic immunity...
October 2013: European Journal of Immunology
Yasuha Arai, Vuong N Bui, Yohei Takeda, Dai Q Trinh, Sayo Nibuno, Jonathan Runstadler, Haruko Ogawa, Kunitoshi Imai
The lung cytokine gene expression profiles of mice infected with 2 strains of H4N8 viruses isolated from shorebirds and reference H4 viruses from ducks are compared. Major differences between the two H4N8 strains of shorebirds, one of which causes a severe respiratory disease in mice, are in the PB1 and NS1 genes. In mice with H4N8 virus induced pneumonia, overall expression of TNF-α, IL-6 and IL-12 genes was markedly higher than in mice infected with other H4 viruses tested, although gene expression of type I interferon was not increased until day 4 post viral infection...
October 2013: Journal of Veterinary Medical Science
Olivier Leymarie, Grégory Jouvion, Pierre-Louis Hervé, Christophe Chevalier, Valérie Lorin, Jérôme Lecardonnel, Bruno Da Costa, Bernard Delmas, Nicolas Escriou, Ronan Le Goffic
The PB1-F2 protein encoded by influenza A viruses can contribute to virulence, a feature that is dependent of its sequence polymorphism. Whereas PB1-F2 from some H1N1 viruses were shown to exacerbate the inflammatory response within the airways, the contribution of PB1-F2 to highly pathogenic avian influenza virus (HPAIV) virulence in mammals remains poorly described. Using a H5N1 HPAIV strain isolated from duck and its PB1-F2 knocked-out mutant, we characterized the dynamics of PB1-F2-associated host response in a murine model of lethal pneumonia...
2013: PloS One
Jason P Lynch, Stuart B Mazzone, Matthew J Rogers, Jaisy J Arikkatt, Zhixuan Loh, Antonia L Pritchard, John W Upham, Simon Phipps
The onset, progression and exacerbations of asthma are frequently associated with viral infections of the lower respiratory tract. An emerging paradigm suggests that this relationship may be underpinned by a defect in the host's antiviral response, typified by the impaired production of type I and type III interferons (IFNs). The failure to control viral burden probably causes damage to the lung architecture and contributes to an aberrant immune response, which together compromise lung function. Although a relatively rare cell type, the plasmacytoid dendritic cell dedicates much of its transcriptome to the synthesis of IFNs and is pre-armed with virus-sensing pattern recognition receptors...
January 2014: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Raquel Almansa, Jesús F Bermejo-Martín, Raúl Ortiz de Lejarazu Leonardo
Three years after the pandemic, major advances have been made in our understanding of the innate and adaptive immune responses to the influenza A(H1N1)pdm09 virus and those responses' contribution to the immunopathology associated with this infection. Severe disease is characterized by early secretion of proinflammatory and immunomodulatory cytokines. This cytokine secretion persisted in patients with severe viral pneumonia and was directly associated with the degree of viral replication in the respiratory tract...
October 2012: Enfermedades Infecciosas y Microbiología Clínica
Bart N Lambrecht, Hamida Hammad
Lung dendritic cells (DCs) bridge innate and adaptive immunity, and depending on context, they also induce a Th1, Th2, or Th17 response to optimally clear infectious threats. Conversely, lung DCs can also mount maladaptive Th2 immune responses to harmless allergens and, in this way, contribute to immunopathology. It is now clear that the various aspects of DC biology can be understood only if we take into account the functional specializations of different DC subsets that are present in the lung in homeostasis or are attracted to the lung as part of the inflammatory response to inhaled noxious stimuli...
2012: Annual Review of Immunology
Daniela Damjanovic, Maziar Divangahi, Kapilan Kugathasan, Cherrie-Lee Small, Anna Zganiacz, Earl G Brown, Cory M Hogaboam, Jack Gauldie, Zhou Xing
Lung immunopathology is the main cause of influenza-mediated morbidity and death, and much of its molecular mechanisms remain unclear. Whereas tumor necrosis factor-α (TNF-α) is traditionally considered a proinflammatory cytokine, its role in influenza immunopathology is unresolved. We have investigated this issue by using a model of acute H1N1 influenza infection established in wild-type and TNF-α-deficient mice and evaluated lung viral clearance, inflammatory responses, and immunopathology. Whereas TNF-α was up-regulated in the lung after influenza infection, it was not required for normal influenza viral clearance...
December 2011: American Journal of Pathology
Sarah McCormick, Christopher R Shaler, Cherrie-Lee Small, Carly Horvath, Daniela Damjanovic, Earl G Brown, Naoko Aoki, Toshiyuki Takai, Zhou Xing
Immunopathology is a major cause of influenza-associated morbidity and mortality worldwide. However, the role and regulatory mechanisms of CD4 T cells in severe lung immunopathology following acute influenza infection are poorly understood. In this paper, we report that the emergence of immunopathogenic CD4 T cells is under the control of a transmembrane immunoadaptor DAP12 pathway during influenza infection. We find that the mice lacking DAP12 have unaltered viral clearance but easily succumb to influenza infection as a result of uncontrolled immunopathology...
October 15, 2011: Journal of Immunology: Official Journal of the American Association of Immunologists
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