The respiratory microbiome and susceptibility to influenza virus infection

Lee, Kyu Han; Gordon, Aubree; Shedden, Kerby; Kuan, Guillermina; Ng, Sophia; Balmaseda, Ángel; Foxman, Betsy

doi:10.1101/372649

Cited by 30 publications

(44 citation statements)

References 43 publications

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“…There is increasing evidence of the important role of the host’s gut microbiome on IAV-specific immunity in the respiratory tract (33, 34). Yet, there is only one study evaluating the role of the URT microbiota in IAV infection (35) and no studies on its effect on transmission. This is surprising given that the nasopharynx, a non-sterile environment extensively colonized by a diverse bacterial flora, is the first location encountered by IAV.…”

Section: Resultsmentioning

confidence: 99%

An infant mouse model of influenza virus transmission demonstrates the role of virus-specific shedding, humoral immunity, and sialidase expression by colonizingStreptococcus pneumoniae

Ortigoza

Blaser

Zafar

et al. 2018

Preprint

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1 9 2 0 2 1 2 2 Word count: Abstract (368), Text (4692) 2 3 2 ABSTRACT 2 4 2 5The pandemic potential of influenza A viruses (IAV) depends on the infectivity of 2 6 the host, transmissibility of the virus, and susceptibility of the recipient. While virus traits 2 7 supporting IAV transmission have been studied in detail using ferret and guinea pig 2 8 models, there is limited understanding of host traits determining transmissibility and 2 9 susceptibility because current animal models of transmission are not sufficiently 3 0 tractable. Although mice remain the primary model to study IAV immunity and 3 1 pathogenesis, the efficiency of IAV transmission in adult mice has been inconsistent. 2Here we describe an infant mouse model which support efficient transmission of IAV. 3We demonstrate that transmission in this model requires young age, close contact, 3 4 shedding of virus particles from the upper respiratory tract (URT) of infected pups, the 3 5 use of a transmissible virus strain, and a susceptible recipient. We characterize 3 6shedding as a marker of infectiousness that predicts the efficiency of transmission 3 7 among different influenza virus strains. We also demonstrate that transmissibility and 3 8 susceptibility to IAV can be inhibited by humoral immunity via maternal-infant transfer of 3 9 IAV-specific immunoglobulins, and modifications to the URT milieu, via sialidase activity 4 0 of colonizing Streptococcus pneumoniae (Spn). Due to its simplicity and efficiency, this 4 1 model can be used to dissect the host's contribution to IAV transmission and explore 4 2 new methods to limit contagion.4 3 3 IMPORTANCE 4 4 4 5This study provides insight into the role of the virus strain, age, immunity, and 4 6 URT flora on IAV shedding and transmission efficiency. Using the infant mouse model, 4 7 we found that: (a) differences in viral shedding of various IAV strains is dependent on 4 8 specific hemagglutinin (HA) and/or neuraminidase (NA) proteins; (b) host age plays a 4 9 key role in the efficiency of IAV transmission; (c) levels of IAV-specific immunoglobulins 5 0 are necessary to limit infectiousness, transmission, and susceptibility to IAV; and (d) 5 1 expression of sialidases by colonizing Spn antagonize transmission by limiting the 5 2 acquisition of IAV in recipient hosts. Our findings highlight the need for strategies that 5 3 limit IAV shedding, and the importance of understanding the function of the URT 5 4 bacterial composition in IAV transmission. This work reinforces the significance of a 5 5tractable animal model to study both viral and host traits affecting IAV contagion, and its 5 6 potential for optimizing vaccines and therapeutics that target disease spread. 5 7 5 8 5 9

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Section: Resultsmentioning

confidence: 99%

An infant mouse model of influenza virus transmission demonstrates the role of virus-specific shedding, humoral immunity, and sialidase expression by colonizingStreptococcus pneumoniae

Ortigoza

Blaser

Zafar

et al. 2018

Preprint

View full text Add to dashboard Cite

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“…In contrast, our cohort includes patients from all age groups, including young and elderly, with a range of disease severity. A recent household transmission study shows that influenza susceptibility is associated with differences in the overall bacterial community structure, with a particularly increased influenza risk in young children (20). These differences between studies suggest that patient characteristics such as age, comorbidities, vaccination status and treatments and viral characteristics need to be considered when studying the effect of influenza infection on the respiratory microbiota.…”

Section: Discussionmentioning

confidence: 99%

Microbial composition of the human nasopharynx varies according to influenza virus type and vaccination status

Ding

Song

Zhou

et al. 2019

Preprint

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“…Indeed, immunity and microbiota of the gut and lungs are closely interlinked . In humans, the microbiome of the upper respiratory tract, including nose and throat, has been shown to change upon influenza infection . Whether intestinal ILC populations are affected in influenza infection in humans has not yet been addressed.…”

Section: Microbiota – Ilc Axis During Infectious Diseasesmentioning

confidence: 99%

“…124 In humans, the microbiome of the upper respiratory tract, including nose and throat, has been shown to change upon influenza infection. 125 Whether intestinal ILC populations are affected in influenza infection in humans has not yet been addressed. However, ILCs, specifically ILC2s, are increased upon infection with influenza A virus (IAV) in the respiratory tract in mice.…”

Section: Microbiota and Ilcs In Viral Infectionsmentioning

confidence: 99%

The interaction of intestinal microbiota and innate lymphoid cells in health and disease throughout life

Ganal‐Vonarburg

Duerr

2019

Immunology

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Summary Immunity is shaped by commensal microbiota. From early life onwards, microbes colonize mucosal surfaces of the body and thereby trigger the establishment of immune homeostasis and defense mechanisms. Recent evidence reveals that the family of innate lymphoid cells (ILCs), which are mainly located in mucosal tissues, are essential in the maintenance of barrier functions as well as in the initiation of an appropriate immune response upon pathogenic infection. In this review, we summarize recent insights on the functional interaction of microbiota and ILCs at steady‐state and throughout life. Furthermore, we will discuss the interplay of ILCs and the microbiota in mucosal infections focusing on intestinal immunity.

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The respiratory microbiome and susceptibility to influenza virus infection

Abstract: 25

Cited by 30 publications

References 43 publications

An infant mouse model of influenza virus transmission demonstrates the role of virus-specific shedding, humoral immunity, and sialidase expression by colonizingStreptococcus pneumoniae

An infant mouse model of influenza virus transmission demonstrates the role of virus-specific shedding, humoral immunity, and sialidase expression by colonizingStreptococcus pneumoniae

Microbial composition of the human nasopharynx varies according to influenza virus type and vaccination status

The interaction of intestinal microbiota and innate lymphoid cells in health and disease throughout life

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