Supplementary Material for: Ficolins Promote Fungal Clearance in vivo and Modulate the Inflammatory Cytokine Response in Host Defense against Aspergillus fumigatus
2016-07-28T11:53:17Z (GMT) by
<i>Aspergillus fumigatus</i> is an opportunistic fungal pathogen that causes severe invasive infections in immunocompromised patients. Innate immunity plays a major role in protection against <i>A. fumigatus.</i> The ficolins are a family of soluble pattern recognition receptors that are capable of activating the lectin pathway of complement. Previous in vitro studies reported that ficolins bind to <i>A. fumigatus</i>, but their part in host defense against fungal infections in vivo is unknown. In this study, we used ficolin-deficient mice to investigate the role of ficolins during lung infection with <i>A. fumigatus</i>. Ficolin knockout mice showed significantly higher fungal loads in the lungs 24 h postinfection compared to wild-type mice. The delayed clearance of <i>A. fumigatus</i> in ficolin knockout mice could not be attributed to a compromised recruitment of inflammatory cells. However, it was revealed that ficolin knockout mice exhibited a decreased production of proinflammatory cytokines in the lungs compared to wild-type mice following <i>A. fumigatus </i>infection. The impaired clearance and cytokine production in ficolin knockout mice was independent of complement, as shown by equivalent levels of <i>A. fumigatus-</i>mediated complement activation in ficolin knockout mice and wild-type mice. In conclusion, this study demonstrates that ficolins are important in initial innate host defense against <i>A. fumigatus</i> infections in vivo.