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Significance Translocation of the nuclear factor (NF)-κB homolog Relish in response to microbial infection is a hallmark of the arthropod immune deficiency (IMD) pathway. Classically, transduction within the IMD molecular cascade is regulated by the inhibitor of apoptosis protein 2 (IAP2). In the Lyme diseaseIxodes scapularis tick, X-linked inhibitor of apoptosis (XIAP) is considered a functionally analogous enzyme. Ticks lack homologs for some genes of the IMD network. As such, substrates of XIAP remain elusive. Here, we identify the molecule p47 as a binding partner of XIAP and Kenny (IKKγ/NEMO). We demonstrate that p47 induces a signaling cascade within the tick IMD pathway to limit microbial infection. This work emphasizes the importance of studying ticks to discover fundamental immunological processes.

p47 licenses activation of the immune deficiency pathway in the tick Ixodes scapularis