Differential Ability of Pandemic and Seasonal H1N1 Influenza A Viruses To Alter the Function of Human Neutrophils.

Scott D. Kobayashi,Vinod Nair,John C. Kash,Frank R. DeLeo,Friederike Feldmann,Natalia Malachowa,Tregei Starr,Brett Freedman,Heinz Feldmann,Daniel E. Sturdevant,Jeffery K. Taubenberger,Olivia Steele-Mortimer

doi:10.1128/mspheredirect.00567-17

Scott D. Kobayashi, Vinod Nair + Show 10 more

Open Access

https://doi.org/10.1128/mspheredirect.00567-17

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Abstract

Neutrophils are essential cells of host innate immunity. Although the role of neutrophils in defense against bacterial and fungal infections is well characterized, there is a relative paucity of information about their role against viral infections. Influenza A virus (IAV) infection can be associated with secondary bacterial coinfection, and it has long been posited that the ability of IAV to alter normal neutrophil function predisposes individuals to secondary bacterial infections. To better understand this phenomenon, we evaluated the interaction of pandemic or seasonal H1N1 IAV with human neutrophils isolated from healthy persons. These viruses were ingested by human neutrophils and elicited changes in neutrophil gene expression that are consistent with an interferon-mediated immune response. The viability of neutrophils following coculture with either pandemic or seasonal H1N1 IAV was similar for up to 18h of culture. Notably, neutrophil exposure to seasonal (but not pandemic) IAV primed these leukocytes for enhanced functions, including production of reactive oxygen species and bactericidal activity. Taken together, our results are at variance with the universal idea that IAV impairs neutrophil function directly to predispose individuals to secondary bacterial infections. Rather, we suggest that some strains of IAV prime neutrophils for enhanced bacterial clearance. IMPORTANCE A long-standing notion is that IAV inhibits normal neutrophil function and thereby predisposes individuals to secondary bacterial infections. Here we report that seasonal H1N1 IAV primes human neutrophils for enhanced killing of Staphylococcus aureus. Moreover, we provide a comprehensive view of the changes in neutrophil gene expression during interaction with seasonal or pandemic IAV and report how these changes relate to functions such as bactericidal activity. This study expands our knowledge of IAV interactions with human neutrophils.

Highlights

Neutrophils are essential cells of host innate immunity
Infections with pandemic H1N1 A/Mexico/4108/2009 (Mex09) Influenza A virus (IAV) produce more severe upper and lower respiratory tract pathology than those caused by seasonal H1N1 A/Kawasaki/UTK-4/2009 (Kaw09) IAV in nonhuman primate infection models [12,13,14]. 2009 pandemic H1N1 IAV strains elicit greater production of cytokines from epithelial cells and trigger greater neutrophil influx into the lung than seasonal IAV strains do [13,14,15]
IAV particles were associated with human neutrophils within 30 min (Fig. 1A)

Summary

Introduction

Neutrophils are essential cells of host innate immunity. the role of neutrophils in defense against bacterial and fungal infections is well characterized, there is a relative paucity of information about their role against viral infections. There was a limited increase in IAV matrix gene transcripts over time, msphere.asm.org 2 Influenza A Virus Alters Human Neutrophil Function especially compared to the increase in viral RNA transcripts in MDCK cells infected at the same multiplicity of infection (MOI) (Fig. 2A).

Results

Conclusion