The immunology of influenza virus-associated bacterial pneumonia

Robinson, Keven M.; Kolls, Jay K.; Alcorn, John F.

doi:10.1016/j.coi.2015.02.002

Cited by 110 publications

(123 citation statements)

References 57 publications

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“…This is probably also the case for co-infections by rhinovirus, adenovirus or parainfluenza and Streptococcus pneumoniae as well as for Haemophilus influenza and Moraxella catarrhalis co-infections 107 . Several mechanisms may contribute to worsen the clinical outcome of these co-infections in that viral infections can compromise immune-driven resistance 97 or tissue damage control 15 mechanisms against bacterial co-infections, as illustrated for influenza virus and Legionella pneumophila co-infections 97 15 .…”

Section: Disease Tolerance To Co-infectionsmentioning

confidence: 92%

“…Pathogen class-specific tissue damage control mechanisms are particularly relevant in the context of co-infections, as illustrated for bacterial pneumonia following influenza virus infection 107 . This is probably also the case for co-infections by rhinovirus, adenovirus or parainfluenza and Streptococcus pneumoniae as well as for Haemophilus influenza and Moraxella catarrhalis co-infections 107 .…”

Section: Disease Tolerance To Co-infectionsmentioning

confidence: 99%

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Disease tolerance and immunity in host protection against infection

2017

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The immune system has most likely evolved to limit the negative impact exerted by pathogens on host homeostasis. This defense strategy relies on the concerted action of innate and adaptive components of the immune system, which sense and target pathogens for containment, destruction or expulsion. Resistance to infection refers to these immune functions, which reduce the pathogen load of an infected host as the means to preserve homeostasis. Immune-driven resistance to infection is coupled to an additional, and arguably as important, defense strategy that limits the extent of dysfunction imposed to host parenchyma tissues during infection, without exerting a direct negative impact on pathogens.This defense strategy, called disease tolerance, relies on tissue damage control mechanisms that prevent the deleterious effects of pathogens, while uncoupling immunedriven resistance mechanisms from immunopathology and disease. Here we provide a unifying view of resistance and disease tolerance within the framework of immunity to infection.

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Section: Disease Tolerance To Co-infectionsmentioning

confidence: 92%

Section: Disease Tolerance To Co-infectionsmentioning

confidence: 99%

Disease tolerance and immunity in host protection against infection

2017

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“…During this time, secondary infection results in increased lung inflammation, impaired Type 17 antibacterial immunity, decreased antimicrobial peptide production, and increased mortality. 55 Interestingly, influenza infection did not exacerbate S. aureus burden at 21 days after infection. Despite similar bacterial clearance, airspace inflammation induced by S. aureus was attenuated in influenza superinfected mice.…”

Section: Recovery From Influenza Infectionmentioning

confidence: 99%

Epigenetic and Transcriptomic Regulation of Lung Repair during Recovery from Influenza Infection

Pociask

Robinson

Chen

et al. 2017

The American Journal of Pathology

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Seasonal and pandemic influenza is a cause of morbidity and mortality worldwide. Most people infected with influenza virus display mild-to-moderate disease phenotypes and recover within a few weeks. Influenza is known to cause persistent alveolitis in animal models; however, little is known about the molecular pathways involved in this phenotype. We challenged C57BL/6 mice with influenza A/PR/8/34 and examined lung pathologic processes and inflammation, as well as transcriptomic and epigenetic changes at 21 to 60 days after infection. Influenza induced persistent parenchymal lung inflammation, alveolar epithelial metaplasia, and epithelial endoplasmic reticulum stress that were evident after the clearance of virus and resolution of morbidity. Influenza infection induced robust changes in the lung transcriptome, including a significant impact on inflammatory and extracellular matrix protein expression. Despite the robust changes in lung gene expression, preceding influenza (21 days) did not exacerbate secondary Staphylococcus aureus infection. Finally, we examined the impact of influenza on miRNA expression in the lung and found an increase in miR-155. miR-155 knockout mice recovered from influenza infection faster than controls and had decreased lung inflammation and endoplasmic reticulum stress. These data illuminate the dynamic molecular changes in the lung in the weeks after influenza infection and characterize the repair process, identifying a novel role for miR-155. (Am J Pathol 2017, 187: 851e863; http://dx

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“…Several studies have illustrated a multifactorial nature of IAV-S. pneumoniae copathogenesis with a plethora of underlying mechanisms (3,20,21). These include virus-mediated immune modulations such as aberrant inflammatory cell recruitment and function as well as increased cell death, often leading to changes in the antipneumococcal cytokine and chemokine responses (22,23).…”

mentioning

confidence: 99%

Influenza A Virus Infection Predisposes Hosts to Secondary Infection with Different Streptococcus pneumoniae Serotypes with Similar Outcome but Serotype-Specific Manifestation

et al. 2016

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e Influenza A virus (IAV) and Streptococcus pneumoniae are major causes of respiratory tract infections, particularly during coinfection. The synergism between these two pathogens is characterized by a complex network of dysregulated immune responses, some of which last until recovery following IAV infection. Despite the high serotype diversity of S. pneumoniae and the serotype replacement observed since the introduction of conjugate vaccines, little is known about pneumococcal strain dependency in the enhanced susceptibility to severe secondary S. pneumoniae infection following IAV infection. Thus, we studied how preinfection with IAV alters host susceptibility to different S. pneumoniae strains with various degrees of invasiveness using a highly invasive serotype 4 strain, an invasive serotype 7F strain, and a carrier serotype 19F strain. A murine model of pneumococcal coinfection during the acute phase of IAV infection showed a significantly increased degree of pneumonia and mortality for all tested pneumococcal strains at otherwise sublethal doses. The incidence and kinetics of systemic dissemination, however, remained bacterial strain dependent. Furthermore, we observed strain-specific alterations in the pulmonary levels of alveolar macrophages, neutrophils, and inflammatory mediators ultimately affecting immunopathology. During the recovery phase following IAV infection, bacterial growth in the lungs and systemic dissemination were enhanced in a strain-dependent manner. Altogether, this study shows that acute IAV infection predisposes the host to lethal S. pneumoniae infection irrespective of the pneumococcal serotype, while the long-lasting synergism between IAV and S. pneumoniae is bacterial strain dependent. These results hold implications for developing tailored therapeutic treatment regimens for dual infections during future IAV outbreaks. Infection with secondary bacterial pathogens is attributed to be the major cause of excessive mortality during influenza A virus (IAV) outbreaks. This lethal synergism has been recognized as early as during the 1918-1919 IAV pandemic with an estimated global death toll of 50 to 100 million (1, 2). Retrospective studies disclosed that 71% of the fatal cases during this pandemic were positive for Streptococcus pneumoniae (also called pneumococcus), providing the first epidemiological evidence for viral-bacterial coinfections (2). A clear predisposition to bacterial disease was also evident in all of the succeeding influenza pandemics, including the more recent 2009 H1N1 outbreak, which had a 10 to 55% higher incidence of hospitalizations and mortality due to bacterial pneumonia (3). Pneumococcal colonization is transient and asymptomatic in immunocompetent individuals and most commonly occurs in early childhood (4). At the same time, however, pneumococci are able to cause a variety of diseases ranging from mild sinusitis and otitis media to more-severe infections like sepsis and meningitis. Even though the introduction of the polyvalent pneumococcal conjugate vaccines...

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The immunology of influenza virus-associated bacterial pneumonia

Cited by 110 publications

References 57 publications

Disease tolerance and immunity in host protection against infection

Disease tolerance and immunity in host protection against infection

Epigenetic and Transcriptomic Regulation of Lung Repair during Recovery from Influenza Infection

Influenza A Virus Infection Predisposes Hosts to Secondary Infection with Different Streptococcus pneumoniae Serotypes with Similar Outcome but Serotype-Specific Manifestation

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