Innate sensors of influenza virus: clues to developing better intranasal vaccines

Abstract

Mucosal immunity acquired by natural infection with influenza viruses at the respiratory tract is more effective and cross-protective against subsequent variant virus infection than systemic immunity induced by parenteral immunization with inactivated vaccines. To develop an effective influenza vaccine, it is beneficial to mimic the process of natural infection that bridges innate and adaptive immune systems. The innate immune system that recognizes influenza virus infection consists of several classes of pattern-recognition receptors, including the Toll-like receptors, the retinoic acid-inducible gene-I-like receptors and the NOD-like receptors. Here, we review our current understanding of the mechanism of innate recognition of influenza and how the signals emanating from the innate sensors control adaptive immunity. Further, we discuss the potential roles of these receptors in developing intranasal influenza vaccines.

Keywords::

• adaptive immune response
• adjuvant
• IL-1β
• inflammasome
• influenza
• innate immune response
• intranasal vaccine
• NALP3
• NOD-like receptor
• RIG-1-like receptor
• Toll-like receptor

Acknowledgements

We would like to acknowledge all of our colleagues for their contributions and apologize to those whose work could not be cited. Also, we appreciate Dr Yasunori Ogura (University of the Ryukyus, Japan) and all members of Iwasaki’s and Hasegawa’s laboratories for the helpful discussions.

Financial & competing interests disclosure

This work was supported by Public Health Service grants from the NIH/NIAID; R01 AI 054359, R01 AI 062428, R01 AI 064705 (to A.I.), and grants from the Ministry of Health, Labor and Welfare, Japan. T Ichinohe is a JSPS Postdoctoral Fellow for Research Abroad. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.