Introduction

About a century ago, Metchnikoff was one of the first to realize that we are endowed with an inherent ability to recognize foreign matter, and moreover, that a similar cell-based defensive system operates in eukaryotic organisms as diverse as humans and "water fleas" (Daphniae). By studying lower organisms, i.e., starfish or water fleas, he observed "phagocytes" cells (e.g., macrophages) could attack foreign objects, ranging from rose thorns to fungal spores, engulfing the latter. The phagocytosis and the subsequent intracellular killing of bacteria were recognized as an essential part of immunity, protecting the host against pathogens that would otherwise destroy it. The principle that the dichotomous relationship between innate or natural immunity and adaptive or acquired immunity, which develops only in vertebrates, depends upon lymphoid cells, and grows stronger with recurrent exposure to antigen, grew from that time. Today we know that the innate immune response is an essential precursor to the adaptive immune response. The primary recognition of microbes therefore falls within the purview of the innate immune system, and for decades, the goal of innate immunologists has been to understand how microbes are recognized; i.e., what receptors are involved, how microbial killing is mediated and how the innate immune cells are able to sound an alarm via systemic mediators.

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