Deep-sea microbes as tools to refine the rules of innate immune pattern recognition

Abstract

The assumption of near-universal bacterial detection by pattern recognition receptors is a foundation of immunology. The limits of this pattern recognition concept, however, remain undefined. As a test of this hypothesis, we determined whether mammalian cells can recognize bacteria that they have never had the natural opportunity to encounter. These bacteria were cultivated from the deep Pacific Ocean, where the genus Moritella was identified as a common constituent of the culturable microbiota. Most deep-sea bacteria contained cell wall lipopolysaccharide (LPS) structures that were expected to be immunostimulatory, and some deep-sea bacteria activated inflammatory responses from mammalian LPS receptors. However, LPS receptors were unable to detect 80% of deep-sea bacteria examined, with LPS acyl chain length being identified as a potential determinant of immunosilence. The inability of immune receptors to detect most bacteria from a different ecosystem suggests that pattern recognition strategies may be defined locally, not globally.

Innate immune detection of lipid oxidation as a threat assessment strategy

“…Other LPS-interacting proteins have been described in detail in recent reviews 13 , 70 . Recently, it was shown that mammalian PRRs are unable to detect the LPS of most bacteria from a different ecosystem, such as deep sea bacteria, despite retaining most structural features of Escherichia coli LPS 71 . These data suggest that pattern recognition of structurally conserved ligands may be defined locally, not globally.…”

Infection-induced membrane ruffling initiates danger and immune signaling via the mechanosensor PIEZO1

“…Some variation in this detection efficiency originates from the co-evolution of PRRs and PAMPs structures. Specifically, some bacteria have evolved to produce less immunogenic PAMPs to avoid immune detection by their host (Fitzgerald and Kagan, 2020;Sansonetti, 2011;Wolf and Underhill, 2018), while PRRs have evolved to optimally recognize PAMPs of bacteria they typically encounter over microbes from remote ecosystems (Gauthier et al, 2021). In contrast, mechanosensing invasion by PIEZO1 makes it possible to identify a highly specific event of infection, which is fully restricted to certain pathogens.…”

Transcriptomic Down-Regulation of Immune System Components in Barrier and Hematopoietic Tissues after Lipopolysaccharide Injection in Antarctic Notothenia coriiceps

“…The lack of TLR response could be linked to the recent observation that TLR5, TLR8, TLR21, TLR22 and TLR23 are under positive selective pressure in Antarctic Notothenioids [41]. Furthermore, a study of deep-sea bacteria revealed pathogen associated molecular patterns (PAMPs) that failed to interact with human TLR, and this was explained by the absence of selective pressure for their recognition during pathogen-recognition receptors (PRR) evolution and so they were "immune silent" [123]. Nonetheless, although the transcriptional response of N. coriiceps to i.p.…”