Our view is that the data underscore the context and/or tissue-dependent nature of IMD signaling and the difference between intracellular control exerted when interacting with the gut microbiota and/or upon infection (dusp36, pgrp-le, pirk, and drybp) (see Thevenon et al., 2009, Bosco-Drayon et al., 2012, Lhocine et al., 2008; and Aparicio et al., 2013; respectively) versus infection-independent homeostatic control (dnr-1, trbd, and tg) (see Cao et al., 2013, Fernando et al., 2014; and Shibata et al., 2013; respectively). The gene discussed is PGLYRP1; the disease is infection.