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Pattern Recognition Molecule Mindin Promotes Intranasal Clearance of Influenza Viruses¹

Department of Immunology, Duke University Medical Center, Durham, NC 27710

The innate immune response is essential for host defense against microbial pathogen infections and is mediated by pattern recognition molecules recognizing pathogen-associated molecular patterns. Our previous work has demonstrated that the extracellular matrix protein mindin functions as a pattern recognition molecule for bacterial pathogens. In this study, we examined the role of mindin in influenza virus infection. We found that intranasal infection of mindin-deficient mice by influenza virus resulted in dramatically increased virus titers in the lung and intranasal cavity of mutant mice. In contrast, lungs from intratracheally infected mindin-deficient mice contained similar influenza virus titers. We showed that mindin interacted with influenza virus particles directly and that mindin-deficient macrophages exhibited impaired activation after influenza virus infection in vitro. Furthermore, intranasal administration of recombinant mindin significantly enhanced the clearance of influenza virus in wild-type mice. Together, these results demonstrate that mindin plays an essential role in the host innate immune response to influenza virus infection and suggest that mindin may be used as an immune-enhancing agent in influenza infection.

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¹ This work was supported by National Institutes of Health Grants AI054658 and AI061364.

² Address correspondence and reprint requests to Dr. You-Wen He, Department of Immunology, Box 3010, Duke University Medical Center, Durham, NC 27710. E-mail address: he000004{at}mc.duke.edu

³ Abbreviations used in this paper: ECM, extracellular matrix; MDCK, Madin-Darby canine kidney; HSA, human serum albumin; DMTAP, 1,2-dimyristoyl-3-trimethylammonium propane; TCID₅₀, 50% tissue culture infection dose; RT, room temperature; HA, hemagglutinination; cRBC, chicken RBC; NALT, nasal-associated lymphoid tissue.