Innate and adaptive humoral responses coat distinct commensal bacteria with immunoglobulin A

Immunoglobulin A (IgA) is prominently secreted at mucosal surfaces and coats a fraction of the intestinal microbiota. However, the commensal bacteria bound by IgA are poorly characterized and the type of humoral immunity they elicit remains elusive. We used bacterial flow cytometry coupled with 16S rRNA gene sequencing (IgA-Seq) in murine models of immunodeficiency to identify IgA-bound bacteria and elucidate mechanisms of commensal IgA targeting. We found that residence in the small intestine, rather than bacterial identity, dictated induction of specific IgA. Most commensals elicited strong T-independent (TI) responses that originated from the orphan B1b lineage and from B2 cells, but excluded natural antibacterial B1a specificities. Atypical commensals including segmented filamentous bacteria and Mucispirillum evaded TI responses but elicited T-dependent IgA. These data demonstrate exquisite targeting of distinct commensal bacteria by multiple layers of humoral immunity and reveal a specialized function of the B1b lineage in TI mucosal IgA responses

A shared Runx1-bound <i>Zbtb16</i> enhancer directs innate and innate-like lymphoid lineage development

Zbtb16-encoded PLZF is a signature transcription factor (TF) that directs the acquisition of T-helper effector programs during the development of multiple innate lymphocyte lineages, including natural killer T cell, innate lymphoid cell, mucosal-associated invariant T cell and γδ lineages. PLZF is also essential in osteoblast and spermatogonial development. How Zbtb16 itself is regulated in different lineages is incompletely understood. Here, by systematic CRISPR/Cas9-assisted deletions of chromatin accessible regions within the Zbtb16 locus in mouse, we identify a critical enhancer controlling PLZF expression exclusively in innate lymphoid lineages. Multiple sites within this enhancer express canonical motifs for the TF Runx1, which is essential for the development of these lineages. Notably, some regulatory sites control the kinetic rather than the overall level of PLZF expression. Thus, our comprehensive, unbiased analysis of regulatory elements in vivo reveals critical mechanisms of Zbtb16 regulation shared between innate and innate-like lymphoid lineages

Isotopes track Tethyan seamount subduction beneath the Troodos spreading centre, Cyprus

Supra-subduction zone volcanoes record the chemical transfer of sedimentary and igneous material from the subducting plate to the overlying mantle and lithosphere. This transfer is thought to preferentially involve fluid-mobile elements, which swamp the signature of similar trace elements in the supra-subduction mantle. Using high-resolution isotope measurements of fluid-mobile Pb, we have traced the evolution and inputs beneath the supra-subduction spreading ridge that is now the Troodos Ophiolite, Cyprus. It is apparent that variable but significant amounts of Pb are actually derived from the mantle wedge, and substantial amounts of the fluid-immobile elements like Nb are introduced from the slab. Our study identifies a chemical transformation of the spreading crust, which reflects a spatial change in the Neo-Tethyan slab. The west was influenced by the subduction of pelagic/carbonate sediments overlying MORB, whereas the east and south also include a high 206Pb/204Pb component, similar to high-μmantle plumes distributed around northern Africa. This chemo-tectonic switch is interpreted to represent the location of supra-subduction spreading relative to the path of a seamount chain colliding with and subducting beneath the Troodos trench. The Hecataeus Rise, located to the southeast of Cyprus, is a candidate to be a foundered relic of this seamount chain, locked in the subduction zone. We also demonstrate that the supra-subduction mantle wedge was of an Atlantic/Pacific-type composition, but the subducting Neo-Tethyan oceanic crust had an Indian Ocean signature. As such, this destructive plate boundary can be defined as the Cretaceous interface between the Atlantic and Indian mantle domains

Mercury and Blood Pressure Levels in Inhabitants from a Highly Industrialized Region in Northern Portugal

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