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

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Science Immunology  12 Mar 2021:
Vol. 6, Issue 57, eabe0531
DOI: 10.1126/sciimmunol.abe0531

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Deep-sea microbes exhibit immunosilence

The innate immune system of mammals uses pattern recognition receptors (PRRs) to detect conserved ligands displayed by potentially pathogenic microbes. To probe the performance of mammalian PRRs when confronted with microbes from a largely foreign ecosystem, Gauthier et al. isolated culturable bacteria from deep-sea Pacific Ocean water samples. Most isolates obtained were Gram-negative Gammaproteobacteria from the Moritella genus. The form of the prototype PRR agonist lipopolysaccharide (LPS) found in the outer membrane of most deep-sea Moritella strains was deficient at engaging with mouse and human LPS-sensing PRRs despite retaining most structural features of LPS from human intestinal E. coli. These findings reveal that the broad recognition powers of PRRs have boundaries that can be violated by a subset of microbes recovered from extreme environments.


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.

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