ABSTRACT
Leptospira interrogans are bacteria that can infect all vertebrates and are responsible for leptospirosis, a neglected zoonosis. Some hosts, such as humans, are susceptible to the disease, whereas mice are resistant and get chronically colonized. Although leptospires escape recognition by some immune receptors, they activate the NOD-like receptor pyrin 3-inflammasome and trigger IL-1ß secretion. Classically, IL-1ß secretion is associated with lytic inflammatory cell death called pyroptosis, resulting from cytosolic LPS binding to inflammatory caspases, such as caspase 11. Interestingly, we showed that L. interrogans and Leptospira biflexa do not trigger cell death in either murine, human, hamster, or bovine macrophages, escaping both pyroptosis and apoptosis. We showed, in murine cells, that the mild IL-1ß secretion induced by leptospires occurred through nonlytic caspase 8-dependent gasdermin D pore formation and not through activation of caspase 11/noncanonical inflammasome. Strikingly, we demonstrated a potent antagonistic effect of pathogenic L. interrogans and their atypical LPS on spontaneous and Escherichia coli LPS-induced cell death. Indeed, LPS of L. interrogans efficiently prevents caspase 11 dimerization and subsequent massive gasdermin D cleavage. Finally, we showed that pyroptosis escape by leptospires prevents massive IL-1ß release, and we consistently found no major role of IL-1R in controlling experimental leptospirosis in vivo. Overall, to our knowledge, our findings described a novel mechanism by which leptospires dampen inflammation, thus potentially contributing to their stealthiness.
Subject(s)
Leptospira interrogans , Leptospirosis , Animals , Cattle , Cricetinae , Humans , Mice , Caspases/metabolism , Gasdermins , Inflammasomes/metabolism , Interleukin-1beta/metabolism , Leptospira interrogans/metabolism , Leptospirosis/metabolism , Leptospirosis/microbiology , Lipopolysaccharides , Macrophages , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pyroptosis , Cell DeathABSTRACT
Deciphering the immune organization of eukaryotes is important for human health and for understanding ecosystems. The recent discovery of antiphage systems revealed that various eukaryotic immune proteins originate from prokaryotic antiphage systems. However, whether bacterial antiphage proteins can illuminate immune organization in eukaryotes remains unexplored. Here, we use a phylogeny-driven approach to uncover eukaryotic immune proteins by searching for homologs of bacterial antiphage systems. We demonstrate that proteins displaying sequence similarity with recently discovered antiphage systems are widespread in eukaryotes and maintain a role in human immunity. Two eukaryotic proteins of the anti-transposon piRNA pathway are evolutionarily linked to the antiphage system Mokosh. Additionally, human GTPases of immunity-associated proteins (GIMAPs) as well as two genes encoded in microsynteny, FHAD1 and CTRC, are respectively related to the Eleos and Lamassu prokaryotic systems and exhibit antiviral activity. Our work illustrates how comparative genomics of immune mechanisms can uncover defense genes in eukaryotes.
ABSTRACT
Central southern Mexico contains highly diverse legumes. In this study, nodule-associated bacteria (NAB) were isolated from wild legume nodules and from nodules on Phaseolus vulgaris plants used as a plant-trap in soils from the same areas as the wild legumes. The bacteria were identified through the 16S rRNA gene sequence analysis, tested for plant growth-promoting (PGP) activities and the production of antimicrobial compounds, and analyzed for potential nodulation by amplifying the nodC gene. Several genera with PGP activity were isolated from legume nodules, including Achromobacter, Acinetobacter, Bacillus, Brevibacillus, Brevibacterium, Burkholderia, Cupriavidus, Dyella, Ensifer, Enterobacter, Herbaspirillum, Kosakonia, Labrys, Microbacterium, Moraxella, Paraburkholderia, Pseudomonas, Rhizobium, Stenotrophomonas; and Aeromonas, Marinococcus Pseudarthrobacter and Pseudoxanthomonas were found in plant legume nodules for the first time. Pseudomonas was the most common bacteria, and Mimosa pudica was colonized by the largest number of genera (6 different genera). A Burkholderia strain from the Burkholderia cepacia complex and a firmicutes strain harbor the nodC gene, identifying them as potential novel nodulating bacteria and showing that most of the strains isolated in this study were NAB. The most frequent PGP activity identified among the strains isolated from wild legumes was IAA synthesis. Two bacteria, Stenotrophomonas sp. and Rhizobium sp., synthesized more than 250 µg/ml, which is more than the level of synthesis reported in this study for Azospirillum brasilense Sp7 (59.77 µg/ml). Nitrogen fixation and antimicrobial compound production were not common, but the production of siderophores was frequently found among all the strains. This study shows that diverse NAB with PGP activity are very common in the legume nodules from central southern Mexico.