Influenza viruses differ in ability to infect macrophages and to induce a local inflammatory response following intraperitoneal injection of mice

Abstract

Strains of influenza A virus show marked differences in their ability to infect murine macrophages (Mφ) such that strain A/PR/8/34 (PR8; H1N1) infects M Mφ poorly while strain BJx109 (H3N2) infects M Mφ to high levels. Given the central role of M Mφ in initiating and regulating inflammatory responses, we hypothesized that virus strains that infect M Mφ poorly may also be poor at initiating inflammatory responses. Studies to compare the inflammatory response of mice after intranasal inoculation with either BJx109 or PR8 were confounded by the rapid growth of the PR8 virus in lung tissues. Consequently, we have characterized the cellular inflammatory response following inoculation into the peritoneal cavity, as influenza viruses do not replicate at this site. Herein, we report marked differences in the local inflammatory response to BJx109 or PR8 in the peritoneal cavity with strain PR8 being particularly poor in its ability to recruit and activate peritoneal leukocytes, including NK cells and M Mφ. In vitro BJx109, but not PR8, stimulated release of high levels of type I IFNs and TNF-α from PEC M Mφ, and treatment of mice with neutralizing antibodies to either cytokine inhibited the ability of BJx109 to recruit and activate NK cells and Ms in the peritoneal cavity. Together, these data suggest that the ability of influenza virus strains to infect M Mφ and stimulate cytokine release is an important factor governing the nature of the acute inflammatory response. © 2010 Australasian Society for Immunology Inc. All rights reserved.