Molecular and environmental aspects of innate immune pattern recognition

Abstract

Since the publication of the Janeway’s pattern recognition hypothesis in 1989, the past 33 years have seen rapid advances in the study of innate immunity, with a focus on pathogen associated molecular patterns (PAMPs) and their stimulatory ability. For good reason, the majority of studies have been conducted in model organisms, but this leaves many open questions about the universality of PAMPs and pattern recognition receptors (PRRs) across living systems. Mammals, for example, have evolved multiple PRRs to detect the PAMP lipopolysaccharide (LPS) from the Gram-negative bacterial outer membrane as a means to distinguish self from non-self and activate innate immunity. Studies in recent years have demonstrated that LPS recognition in mammals is dependent on the structure of its lipid A anchor and that LPS is not immunostimulatory in all eukaryotes. As such, I conducted primary research presented in the following chapters that first addresses the universality of mammalian lipid A pattern recognition using Gram-negative bacteria cultured from the deep sea. Based on this study, I hypothesized that mammals evolved to detect lipid A from Gram-negative bacteria local to their environment. To test this hypothesis in the reverse direction, I addressed the ability of invertebrates inhabiting the deep sea to mount a host response to local Gram-negative bacteria. The results of this study suggested that deep-sea invertebrates may detect local Gram-negative bacteria independent of LPS, thus supporting the hypothesis that innate immunity is locally defined as well as highlighting that LPS is not a universal PAMP in all eukaryotes.