Halophilic Archaea Halorhabdus Rudnickae and Natrinema Salaciae Activate Human Dendritic Cells and Orient T Helper Cell Responses

Abstract

Halophilic archaea are procaryotic organisms distinct from bacteria, known to thrive in hypersaline environments, including salt lakes, salterns, brines and salty food. They have also been identified in the human microbiome. The biological significance of halophiles for human health has rarely been examined. The interactions between halophilic archaea and human dendritic cells (DCs) and T cells have not been identified so far. Here, we show for the first time that the halophilic archaea Halorhabdus rudnickae and Natrinema salaciae activate human monocyte-derived DCs, induce DC maturation, cytokine production and autologous T cell activation. In vitro both strains induced DC up-regulation of the cell-surface receptors CD86, CD80 and CD83, and cytokine production, including IL-12p40, IL-10 and TNF-α, but not IL-23 and IL-12p70. Furthermore, autologous CD4+ T cells produced significantly higher amounts of IFN-γ and IL-13, but not IL-17A when co-cultured with halophile-stimulated DCs in comparison to T cells co-cultured with unstimulated DCs. IFN-γ was almost exclusively produced by naïve T cells, while IL-13 was produced by both naïve and memory CD4+ T cells. Our findings thus show that halophilic archaea are recognized by human DCs and are able to induce a balanced cytokine response. The immunomodulatory functions of halophilic archaea and their potential ability to re-establish the immune balance may perhaps participate in the beneficial effects of halotherapies.

Alterations in Gut Archaea Composition and Their Bacterial Interactions Linked to Hypertension

“…Halorhabdus utahensis, a member of the Halorhabdus genus, can metabolize and produce carotenoids, which have antioxidant properties [27]. Halorhabdus rudnickae has been shown to activate human dendritic cells and orient T helper cell responses [28]. Additionally, metabolites secreted by Halorhabdus rudnickae exhibit significant toxic effects on ovarian cancer cells, suggesting that it plays a protective role as an archaeon [29].…”

Cytotoxic effects of halophilic archaea metabolites on ovarian cancer cell lines

“…salaciae [19]. We chose these two strains because their genome sequences have been determined (accessible at GenBank assembly under the number GCA_900880625.1 and GCA_900110865.1, respectively), and we had already characterized their interaction with innate immune cells [20]. The metabolites of these strains were active on three ovarian cancer cell lines frequently used to study ovarian carcinoma: the cisplatin-sensitive ovarian tumor cell line A2780 and the corresponding cisplatin-resistant A2780cis cell line, as well as the cisplatin-resistant and highly invasive SK-OV-3 cell line, originating from ascites [21][22][23].…”

The Embodied Microbiome

“…Extremophiles in the microbiome are not just niche novelties. Krawczyk et al [128] showed that the halophilic archaea Halorhabdus rudnickae and Natrinema salaciae (which are related to those found in our own microbiome) are able to work through dendritic cells to provide immunoregulation of T cell responses producing a balanced cytokine profile. These findings suggest that similar halophilic archaea may provide a useful function in the human gut.…”

“…Table 4 [123][124][125][126][127][128][129][130][131][132][133][134][135][136][137][138][139][140][141][142] illustrates two fundamental principles about our connection to microbes: 1) We are intimately connected to Earth's microbes, 2) Even if much of our microbiome has some stability, we are constantly exchanging microbes, microbial genes, physiologically-modifying chemicals, and gathering information from and sharing information with the microbes beyond our body. The human body is open to the environment.…”

“…Archaea Halobacteriota (skin) [126][127][128] Alpine Permian-era bore core of a salt deposit, hypersaline-deep lake Antarctica, Solar salterns, Survives space launches, space conditions above the ozone layer as well as Mars-like conditions Polyextremophilic with tolerance of saturating salinity, anaerobic conditions, high levels of ultraviolet and ionizing radiation, subzero temperatures, desiccation, and toxic ions.…”