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?? T cells compose a developmentally regulated intrauterine population and protect against vaginal candidiasis.

ABSTRACT: This most comprehensive analysis to date of ?? T cells in the murine uterus reveals them to compose a unique local T-cell compartment. Consistent with earlier reports, most cells expressed a canonical V?6V?1 TCR, and produced interleukin (IL)-17A upon stimulation. Nonetheless, contrasting with earlier reports, uterine ?? T cells were not obviously intraepithelial, being more akin to sub-epithelial V?6V?1⁺ T cells at several other anatomical sites. By contrast to other tissues however, the uterine compartment also included non-V?6⁺, IFN-?-producing cells; was strikingly enriched in young mice; expressed genes hitherto associated with the uterus, including the progesterone receptor; and did not require microbes for development and/or maintenance. This notwithstanding, ?? T-cell deficiency severely impaired resistance to reproductive tract infection by Candida albicans, associated with decreased responses of IL-17-dependent neutrophils. These findings emphasise tissue-specific complexities of different mucosal ?? cell compartments, and their evident importance in lymphoid stress-surveillance against barrier infection.

SUBMITTER: Monin L

PROVIDER: S-EPMC7567646 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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γδ T cells compose a developmentally regulated intrauterine population and protect against vaginal candidiasis.

Monin L L Ushakov D S DS Arnesen H H Bah N N Jandke A A Muñoz-Ruiz M M Carvalho J J Joseph S S Almeida B C BC Green M J MJ Nye E E Hatano S S Yoshikai Y Y Curtis M M Carlsen H H Steinhoff U U Boysen P P Hayday A A

Mucosal immunology 20200529 6

This most comprehensive analysis to date of γδ T cells in the murine uterus reveals them to compose a unique local T-cell compartment. Consistent with earlier reports, most cells expressed a canonical Vγ6Vδ1 TCR, and produced interleukin (IL)-17A upon stimulation. Nonetheless, contrasting with earlier reports, uterine γδ T cells were not obviously intraepithelial, being more akin to sub-epithelial Vγ6Vδ1<sup>+</sup> T cells at several other anatomical sites. By contrast to other tissues however, ...[more]

PMID: 32472066

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Project description:Plant cell walls contain a renewable, nearly limitless supply of sugar that could be used to support microbial production of commodity chemicals and biofuels. Imidazolium ionic liquid (IIL) solvents are among the best reagents for gaining access to the sugars in this otherwise recalcitrant biomass. However, the sugars from IIL-treated biomass are inevitably contaminated with residual IILs that inhibit growth in bacteria and yeast, blocking biochemical production by these organisms. IIL toxicity is, therefore, a critical roadblock in many industrial biosynthetic pathways. Although several IIL-tolerant (IILT) bacterial and yeast isolates have been identified in nature, few genetic mechanisms have been identified. In this study, we identified two IILTBacillus isolates as well as a spontaneous IILTEscherichia coli lab strain that are tolerant to high levels of two widely used IILs. We demonstrate that all three IILT strains contain one or more pumps of the small multidrug resistance (SMR) family, and two of these strains contain mutations that affect an adjacent regulatory guanidine riboswitch. Furthermore, we show that the regulation of E. colisugE by the guanidine II riboswitch can be exploited to promote IIL tolerance by the simple addition of guanidine to the medium. Our results demonstrate the critical role that transporter genes play in IIL tolerance in their native bacterial hosts. The study presented here is another step in engineering IIL tolerance into industrial strains toward overcoming this key gap in biofuels and industrial biochemical production processes.IMPORTANCE This study identifies bacteria that are tolerant to ionic liquid solvents used in the production of biofuels and industrial biochemicals. For industrial microbiology, it is essential to find less-harmful reagents and microbes that are resistant to their cytotoxic effects. We identified a family of small multidrug resistance efflux transporters, which are responsible for the tolerance of these strains. We also found that this resistance can be caused by mutations in the sequences of guanidine-specific riboswitches that regulate these efflux pumps. Extending this knowledge, we demonstrated that guanidine itself can promote ionic liquid tolerance. Our findings will inform genetic engineering strategies that improve conversion of cellulosic sugars into biofuels and biochemicals in processes where low concentrations of ionic liquids surpass bacterial tolerance.

Dataset Information

?? T cells compose a developmentally regulated intrauterine population and protect against vaginal candidiasis.

Publications

γδ T cells compose a developmentally regulated intrauterine population and protect against vaginal candidiasis.

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