Here, we demonstrated that macrophages derived from Smurf1−/− mice secreted increased levels of the proinflammatory mediators TNF and CXCL1 in vitro, and the lungs from Smurf1−/− mice presented higher ratios of macrophages and neutrophils positive for TNF and iNOS upon infection with MHV-A59. Here, TNF is linked to infection.