The requirement of HOIL-1 for the induction of protective inflammatory cytokines, TNFα, IL-6 and IL-12, following infection of macrophages with Listeria in vitro is consistent with reports that LUBAC is required for efficient NF-κB activation following TLR engagement (Zak et al., 2011; Boisson et al., 2012), but not with a recent report that NF-κB activation following stimulation of TLR4 and TNF-R1 on macrophages by LPS and TNFα, respectively, is unaffected by HOIL-1 deficiency (Rodgers et al., 2014). Here, TLR4 is linked to infection.