Surveillance Immunity: An Emerging Paradigm of Innate Defense Activation in Caenorhabditis elegans

The evolution of bacterivorous nematodes, such as Caenorhabditis elegans, has been shaped by interactions with environmental microbes, which for nematodes are both sources of food and agents of disease. As a result, C. elegans has evolved protective host responses coordinated through multiple pathways, which are required for host survival during microbial infection. Following exposure to a pathogen, putative immune effectors are transcriptionally up-regulated, which has led to an extensive search for the mechanisms underlying pathogen recognition in this simple metazoan host. Biological rationale for the existence of inducible immune defenses has come from the recognition that physiologic [1,2] or aberrant [3] activation of immune responses constitutes an important source of cellular stress for nematodes, arguing that these protective host responses must be tightly regulated to ensure host survival. However, despite much effort, the mechanisms underlying the activation and regulation of immune pathways in nematodes have, until recently, been elusive. In mammals, binding of conserved microbial molecules (so-called microbe-associated molecular patterns, or MAMPs) to cell surface pattern-recognition receptors (e.g., toll-like receptors) is a major method of pathogen detection. Such mechanisms may operate in nematodes [4–6], but a bona fide MAMP and its receptor have yet to be characterized in worms. Recently, a number of studies have supported the hypothesis that the nematode monitors for perturbations in host physiology that accompany infection with pathogenic microbes or the effects of their secreted toxins [7–9]. A related concept was originally pioneered in studies of plant immunity, where it is often called effector-triggered immunity. The major emerging theme here is that the mechanisms of surveillance immunity, as they are referred to in this review, are molded by the strategies employed by microbes to cause disease in the host (Fig 1).