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Toll-like receptor pre-stimulation protects mice against lethal infection with highly pathogenic influenza viruses

Kyoko Shinya12*, Tadashi Okamura2, Setsuko Sueta2, Noriyuki Kasai2, Motoko Tanaka1, Teridah E Ginting1, Akiko Makino1, Amie J Eisfeld3 and Yoshihiro Kawaoka134*

Author Affiliations

1 Department of Microbiology and Infectious Diseases, Graduate School of Medicine, Kobe University, Kobe 650-0017, Japan

2 Institute for Animal Experimentation, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan

3 Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA

4 Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan ERATO Infection-Induced Host Responses Project, Japan Science and Technology Agency, Saitama 332-0012, Japan

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Virology Journal 2011, 8:97  doi:10.1186/1743-422X-8-97

Published: 4 March 2011

Abstract

Since the beginning of the 20th century, humans have experienced four influenza pandemics, including the devastating 1918 'Spanish influenza'. Moreover, H5N1 highly pathogenic avian influenza (HPAI) viruses are currently spreading worldwide, although they are not yet efficiently transmitted among humans. While the threat of a global pandemic involving a highly pathogenic influenza virus strain looms large, our mechanisms to address such a catastrophe remain limited. Here, we show that pre-stimulation of Toll-like receptors (TLRs) 2 and 4 increased resistance against influenza viruses known to induce high pathogenicity in animal models. Our data emphasize the complexity of the host response against different influenza viruses, and suggest that TLR agonists might be utilized to protect against lethality associated with highly pathogenic influenza virus infection in humans.