Lymphopenia Associated with Highly Virulent H5N1 Virus Infection Due to Plasmacytoid Dendritic Cell–Mediated Apoptosis of T Cells

Boonnak, Kobporn; Vogel, Leatrice; Feldmann, Friederike; Feldmann, Heinz; Legge, Kevin L.; Subbarao, Kanta

doi:10.4049/jimmunol.1302992

Cited by 55 publications

(63 citation statements)

References 35 publications

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“…Additionally, severe respiratory virus infection can induce acute respiratory disease syndrome (ARDS), which is associated with significant epithelial-endothelial dysfunction and excessive activation of macrophages and neutrophils (104). ARDS has been observed during experimental IAV infection of animal models, as well as in people naturally infected with highly pathological IAV isolates, such as the 1918 H1N1 "Spanish" influenza strain and the recent zoonotic outbreaks of avian H5N1 and H7N9 IAV strains (105)(106)(107). An eloquent transcriptome analysis by Josset et al, which compared highly pathological versus seasonal IAV infections, detected a strong transcriptional signature of macrophages and neutrophils in the lungs of mice with severe IAV infection (108), which fits with prior histological observations (16).…”

Section: Role Of Mast Cells In Allergies and Asthmamentioning

confidence: 99%

Mast Cells and Influenza A Virus: Association with Allergic Responses and Beyond

2015

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Influenza A virus (IAV) is a widespread infectious agent commonly found in mammalian and avian species. In humans, IAV is a respiratory pathogen that causes seasonal infections associated with significant morbidity in young and elderly populations, and has a large economic impact. Moreover, IAV has the potential to cause both zoonotic spillover infection and global pandemics, which have significantly greater morbidity and mortality across all ages. The pathology associated with these pandemic and spillover infections appear to be the result of an excessive inflammatory response leading to severe lung damage, which likely predisposes the lungs for secondary bacterial infections. The lung is protected from pathogens by alveolar epithelial cells, endothelial cells, tissue resident alveolar macrophages, dendritic cells, and mast cells. The importance of mast cells during bacterial and parasitic infections has been extensively studied; yet, the role of these hematopoietic cells during viral infections is only beginning to emerge. Recently, it has been shown that mast cells can be directly activated in response to IAV, releasing mediators such histamine, proteases, leukotrienes, inflammatory cytokines, and antiviral chemokines, which participate in the excessive inflammatory and pathological response observed during IAV infections. In this review, we will examine the relationship between mast cells and IAV, and discuss the role of mast cells as a potential drug target during highly pathological IAV infections. Finally, we proposed an emerging role for mast cells in other viral infections associated with significant host pathology.

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Section: Role Of Mast Cells In Allergies and Asthmamentioning

confidence: 99%

Mast Cells and Influenza A Virus: Association with Allergic Responses and Beyond

2015

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“…One was recovered from a fatal human infection associated with lymphopenia; this virus caused lymphopenia and was lethal for mice. The other virus was isolated from a nonfatal human case without lymphopenia; this virus replicated in the lungs of mice but was not associated with lymphopenia or lethality (32). We found that lethal H5N1 infection enhanced Fas ligand (FasL) expression on plasmacytoid DCs (pDCs), resulting in apoptosis of influenza-specific CD8 + T cells via a Fas-FasL-mediated pathway; this was not seen in mice infected with the nonlethal H5N1 strain (32).…”

Section: Pathogenesis Of Severe Diseasementioning

confidence: 89%

“…31). Infection of DCs by IAVs does not normally result in cell death or productive viral infection, but HP H5N1 avian IAV can cause productive infection and can also kill certain human DC subsets (32,33).…”

Section: The Immune Response To Iavsmentioning

confidence: 99%

Immune Responses to Avian Influenza Viruses

Koutsakos

Kedzierska

Subbarao

2019

The Journal of Immunology

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Avian influenza A viruses (IAVs) naturally infect different avian species, and aquatic birds are their natural reservoir. Sporadically, avian IAVs can be transmitted to humans, and some, such as H5N1 and H7N9 viruses, cause severe disease in humans. Antigenically novel avian influenza viruses that infect and cause disease in humans pose a potential pandemic threat if they are able to spread efficiently from person to person. The immune response of the host is crucial in determining disease pathogenesis and is the basis for the development of control strategies. In this review, we examine the innate and adaptive immune responses to avian influenza viruses and their role in disease and recovery. Furthermore, we discuss the progress in developing vaccines against avian IAVs and summarize obstacles in designing universal and pandemic influenza vaccines.

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“…Lymphopenia was strongly associated with a higher chance of death in our ndings. Previous studies implied that lymphopenia can have a prognostic value in viral infections (51), and a recent study reported that COVID-19 patients with low blood lymphocyte percentages had poor outcomes (5, 52).…”

Section: Laboratory and Radiologic Ndingsmentioning

confidence: 99%

Clinical, laboratory, and radiologic findings associated with mortality in COVID-19: A systematic review and meta-analysis

Rhim

Park

Lee

et al. 2020

Preprint

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Abstract Although there has been a surge in reports on coronavirus disease 2019 (COVID-19), the clinical signs and findings associated with fatal outcomes have rarely been studied. This systematic review and meta-analysis aimed to investigate the clinical, laboratory, and radiologic features associated with mortality in COVID-19. A comprehensive search was performed using PubMed, Embase, Web of Science, and other databases including government sources, for articles and reports published until May 1, 2020. We extracted the number of events (mortality and non-mortality) from case series and case-control and cross-sectional studies. Hazard ratios (HR) of each finding were extracted from studies with time-to-outcome analysis. In total, 23 studies met the inclusion criteria. Of them, 18 studies were case-control, cross-sectional, and case series study. Whereas, only 5 studies included time-to-outcome analysis. Male sex, age over 80 years, dyspnea, cardiovascular disease, chronic kidney disease, increased troponin I level, acute respiratory distress syndrome, acute kidney injury, and need of invasive mechanical ventilation were significantly associated with mortality. The identification of patients at higher risk of mortality has an utmost importance to achieve better treatment outcomes. The findings from our study may aid the prioritization in times of severe shortages of medical resources. Further studies analyzing diverse demographic and geographic populations are needed to generalize the findings from this study.

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Lymphopenia Associated with Highly Virulent H5N1 Virus Infection Due to Plasmacytoid Dendritic Cell–Mediated Apoptosis of T Cells

Cited by 55 publications

References 35 publications

Mast Cells and Influenza A Virus: Association with Allergic Responses and Beyond

Mast Cells and Influenza A Virus: Association with Allergic Responses and Beyond

Immune Responses to Avian Influenza Viruses

Clinical, laboratory, and radiologic findings associated with mortality in COVID-19: A systematic review and meta-analysis

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