Eosinophils Promote Antiviral Immunity in Mice Infected with Influenza A Virus

Samarasinghe, Amali E.; Melo, Rossana C. N.; Duan, Susu; LeMessurier, Kim S.; Liedmann, Swantje; Surman, Sherri L.; Lee, James J.; Hurwitz, Julia L.; Thomas, Paul G.; McCullers, Jonathan A.

doi:10.4049/jimmunol.1600787

Cited by 140 publications

(176 citation statements)

References 67 publications

(69 reference statements)

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“…Lazarevic et al, 2013). Increased neutrophils and eosinophils in T-bet À/À lungs may also play compensatory roles to other immune cells following influenza virus infection (Fujisawa, 2008;Tate et al, 2011;Hufford et al, 2012;Samarasinghe et al, 2017). All these immune responses are crucial against viral infections, yet surprisingly, the loss of T-bet did not result in marked deficiency in defence against the influenza virus.…”

Section: Discussionmentioning

confidence: 99%

Loss of T‐bet confers survival advantage to influenza–bacterial superinfection

Koean

Ding

2018

The EMBO Journal

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The transcription factor, T‐bet, regulates type 1 inflammatory responses against a range of infections. Here, we demonstrate a previously unaddressed role of T‐bet, to influenza virus and bacterial superinfection. Interestingly, we found that T‐bet deficiency did not adversely affect the efficacy of viral clearance or recovery compared to wild‐type hosts. Instead, increased infiltration of neutrophils and production of Th17 cytokines (IL‐17 and IL‐22), in lungs of influenza virus‐infected T‐bet−/− mice, were correlated with survival advantage against subsequent infection by Streptococcus pneumoniae. Neutralization of IL‐17, but not IL‐22, in T‐bet−/− mice increased pulmonary bacterial load, concomitant with decreased neutrophil infiltration and reduced survival of T‐bet−/− mice. IL‐17 production by CD8+, CD4+ and γδ T cell types was identified to contribute to this protection against bacterial superinfection. We further showed that neutrophil depletion in T‐bet−/− lungs increased pulmonary bacterial burden. These results thus indicate that despite the loss of T‐bet, immune defences required for influenza viral clearance are fully functional, which in turn enhances protective type 17 immune responses against lethal bacterial superinfections.

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Section: Discussionmentioning

confidence: 99%

Loss of T‐bet confers survival advantage to influenza–bacterial superinfection

Koean

Ding

2018

The EMBO Journal

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“…One study demonstrated that H1N1 virus infection can induce the degranulation and facilitate the activation and proliferation of CD8 T cells in vitro . In this work, adoptive transfer of eosinophils from infected animals could protect the recipients against influenza challenge by enhancing antigen-specific cellular responses [114]. The combination of these immune regulatory and enhancing functions with the known effects of eosinophils on lung function requires further studies to determine the relative contributions of each activity and the regulatory role of IL-5 in these processes.…”

Section: Cytokines Induced By Immune Responses (Secondary Cytokines)mentioning

confidence: 99%

New fronts emerge in the influenza cytokine storm

2017

Self Cite

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Influenza virus is a significant pathogen in humans and animals with the ability to cause extensive morbidity and mortality. Exuberant immune responses induced following infection have been described as a “cytokine storm”, associated with excessive levels of proinflammatory cytokines and widespread tissue damage. Recent studies have painted a more complex picture of cytokine networks and their contributions to clinical outcomes. While many cytokines clearly inflict immunopathology, others have non-pathological delimited roles in sending alarm signals, facilitating viral clearance, and promoting tissue repair, such as the IL-33 – amphiregulin axis, which plays a key role in resolving some types of lung damage. Recent literature suggests that type 2 cytokines, traditionally thought of as not involved in anti-influenza immunity, may play an important regulatory role. Here we discuss the diverse roles played by cytokines after influenza infection and highlight new, serene features of the cytokine storm, while highlighting the specific functions of relevant cytokines that perform unique immune functions and may have applications for influenza therapy.

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“…Eosinophils have been shown to exhibit phenotypic changes in response to signals from the extracellular matrix in murine asthma models . They can recruit Th2 CD4 + T cells, activate dendritic cells, polarize M2 macrophages cause nerve cell branching, recruit and activate CD8 T cells, and secrete nerve growth factor or eosinophil peroxidase which activate mast cells through TrkA or Mas‐related gene X2 (MrgX2) receptors, respectively. The interactions between eosinophils and other cells are just starting to be explored in humans.…”

Section: Resultsmentioning

confidence: 99%

Revisiting the NIH Taskforce on the Research needs of Eosinophil-Associated Diseases (RE-TREAD)

Khoury

Akuthota

Ackerman

et al. 2018

Journal of Leukocyte Biology

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Eosinophil-associated diseases (EADs) are rare, heterogeneous disorders characterized by the presence of eosinophils in tissues and/or peripheral blood resulting in immunopathology. The heterogeneity of tissue involvement, lack of sufficient animal models, technical challenges in working with eosinophils, and lack of standardized histopathologic approaches have hampered progress in basic research. Additionally, clinical trials and drug development for rare EADs are limited by the lack of primary and surrogate endpoints, biomarkers, and validated patient-reported outcomes. Researchers with expertise in eosinophil biology and eosinophil-related diseases reviewed the state of current eosinophil research, resources, progress, and unmet needs in the field since the 2012 meeting of the NIH Taskforce on the Research of Eosinophil-Associated Diseases (TREAD). RE-TREAD focused on gaps in basic science, translational, and clinical research on eosinophils and eosinophil-related pathogenesis. Improved recapitulation of human eosinophil biology and pathogenesis in murine models was felt to be of importance. Characterization of eosinophil phenotypes, the role of eosinophil subsets in tissues, identification of biomarkers of eosinophil activation and tissue load, and a better understanding of the role of eosinophils in human disease were prioritized. Finally, an unmet need for tools for use in clinical trials was emphasized. Histopathologic scoring, patient- and clinician-reported outcomes, and appropriate coding were deemed of paramount importance for research collaborations, drug development, and approval by regulatory agencies. Further exploration of the eosinophil genome, epigenome, and proteome was also encouraged. Although progress has been made since 2012, unmet needs in eosinophil research remain a priority.

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Eosinophils Promote Antiviral Immunity in Mice Infected with Influenza A Virus

Cited by 140 publications

References 67 publications

Loss of T‐bet confers survival advantage to influenza–bacterial superinfection

Loss of T‐bet confers survival advantage to influenza–bacterial superinfection

New fronts emerge in the influenza cytokine storm

Revisiting the NIH Taskforce on the Research needs of Eosinophil-Associated Diseases (RE-TREAD)

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