We take advantage of the wealth of rotation measures data contained in the NRAO VLA Sky Survey catalog to derive new, statistically robust, upper limits on the strength of extragalactic magnetic ...fields. We simulate the extragalactic magnetic field contribution to the rotation measures for a given field strength and correlation length, by assuming that the electron density follows the distribution of Lyman-α clouds. Based on the observation that rotation measures from distant radio sources do not exhibit any trend with redshift, while the extragalactic contribution instead grows with distance, we constrain fields with Jeans' length coherence length to be below 1.7 nG at the 2σ level, and fields coherent across the entire observable Universe below 0.65 nG. These limits do not depend on the particular origin of these cosmological fields.
The hallmark features of type 2 mucosal immunity include intestinal tuft and goblet cell expansion initiated by tuft cell activation. How infectious agents that induce type 2 mucosal immunity are ...detected by tuft cells is unknown. Published microarray analysis suggested that succinate receptor 1 (Sucnr1) is specifically expressed in tuft cells. Thus, we hypothesized that the succinate–Sucnr1 axis may be utilized by tuft cells to detect certain infectious agents. Here we confirmed that Sucnr1 is specifically expressed in intestinal tuft cells but not in other types of intestinal epithelial cells, and demonstrated that dietary succinate induces tuft and goblet cell hyperplasia via Sucnr1 and the tuft cell-expressed chemosensory signaling elements gustducin and Trpm5. Conventional mice with a genetic Sucnr1 deficiency (Sucnr1
−/−) showed diminished immune responses to treatment with polyethylene glycol and streptomycin, which are known to enhance microbiota-derived succinate, but responded normally to inoculation with the parasitic worm Nippostrongylus brasiliensis that also produces succinate. Thus, Sucnr1 is required for microbiota-induced but not for a generalized worm-induced type 2 immunity.
Innate lymphoid cells (ILCs) are innate counterparts of adaptive T lymphocytes, contributing to host defense, tissue repair, metabolic homeostasis, and inflammatory diseases. ILCs have been ...considered to be tissue-resident cells, but whether ILCs move between tissue sites during infection has been unclear. We show here that interleukin-25- or helminth-induced inflammatory ILC2s are circulating cells that arise from resting ILC2s residing in intestinal lamina propria. They migrate to diverse tissues based on sphingosine 1-phosphate (S1P)-mediated chemotaxis that promotes lymphatic entry, blood circulation, and accumulation in peripheral sites, including the lung, where they contribute to anti-helminth defense and tissue repair. This ILC2 expansion and migration is a behavioral parallel to the antigen-driven proliferation and migration of adaptive lymphocytes to effector sites and indicates that ILCs complement adaptive immunity by providing both local and distant tissue protection during infection.
Alternative (M2) activation of macrophages driven via the α-chain of the receptor for interleukin 4 (IL-4Rα) is important for immunity to parasites, wound healing, the prevention of atherosclerosis ...and metabolic homeostasis. M2 polarization is dependent on fatty acid oxidation (FAO), but the source of the fatty acids that support this metabolic program has not been clear. We found that the uptake of triacylglycerol substrates via the scavenger receptor CD36 and their subsequent lipolysis by lysosomal acid lipase (LAL) was important for the engagement of elevated oxidative phosphorylation, enhanced spare respiratory capacity (SRC), prolonged survival and expression of genes that together define M2 activation. Inhibition of lipolysis suppressed M2 activation during infection with a parasitic helminth and blocked protective responses to this pathogen. Our findings delineate a critical role for cell-intrinsic lysosomal lipolysis in M2 activation.
Innate lymphoid cells (ILCs) are important for mucosal immunity. The intestine harbors all ILC subsets, but how these cells are balanced to achieve immune homeostasis and mount appropriate responses ...during infection remains elusive. Here, we show that aryl hydrocarbon receptor (Ahr) expression in the gut regulates ILC balance. Among ILCs, Ahr is most highly expressed by gut ILC2s and controls chromatin accessibility at the Ahr locus via positive feedback. Ahr signaling suppresses Gfi1 transcription-factor-mediated expression of the interleukin-33 (IL-33) receptor ST2 in ILC2s and expression of ILC2 effector molecules IL-5, IL-13, and amphiregulin in a cell-intrinsic manner. Ablation of Ahr enhances anti-helminth immunity in the gut, whereas genetic or pharmacological activation of Ahr suppresses ILC2 function but enhances ILC3 maintenance to protect the host from Citrobacter rodentium infection. Thus, the host regulates the gut ILC2-ILC3 balance by engaging the Ahr pathway to mount appropriate immunity against various pathogens.
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•Unique Ahr chromatin features mark gut adaptation of Ahr expression in ILC2s•Ahr inhibits ILC2 function in a cell-intrinsic manner•Genetic ablation of Ahr enhances gut ILC2 function during anti-helminth immunity•Cell-specific activation of Ahr enhances gut ILC3 function in anti-bacterial immunity
The aryl hydrocarbon receptor (Ahr) promotes ILC3 maintenance and function. Li et al. report that Ahr restricts intestinal ILC2 function in a cell-intrinsic manner, suggesting a central role for gut adaptation of Ahr expression in regulating the ILC2-ILC3 balance.
Neutrophils are the first line of defense at the site of an infection. They encounter and kill microbes intracellularly upon phagocytosis or extracellularly by degranulation of antimicrobial proteins ...and the release of Neutrophil Extracellular Traps (NETs). NETs were shown to ensnare and kill microbes. However, their complete protein composition and the antimicrobial mechanism are not well understood. Using a proteomic approach, we identified 24 NET-associated proteins. Quantitative analysis of these proteins and high resolution electron microscopy showed that NETs consist of modified nucleosomes and a stringent selection of other proteins. In contrast to previous results, we found several NET proteins that are cytoplasmic in unstimulated neutrophils. We demonstrated that of those proteins, the antimicrobial heterodimer calprotectin is released in NETs as the major antifungal component. Absence of calprotectin in NETs resulted in complete loss of antifungal activity in vitro. Analysis of three different Candida albicans in vivo infection models indicated that NET formation is a hitherto unrecognized route of calprotectin release. By comparing wild-type and calprotectin-deficient animals we found that calprotectin is crucial for the clearance of infection. Taken together, the present investigations confirmed the antifungal activity of calprotectin in vitro and, moreover, demonstrated that it contributes to effective host defense against C. albicans in vivo. We showed for the first time that a proportion of calprotectin is bound to NETs in vitro and in vivo.
Moiré heterostructures of transition metal dichalcogenides (TMDs) exhibit Mott-insulating behavior both at half filling as well as at fractional fillings, where electronic degrees of freedom form ...self-organized Wigner crystal states. An open question concerns magnetic states obtained by lifting the pseudospin-1/2 degeneracy of these states at lowest temperatures. While at half filling virtual hopping is expected to induce (weak) antiferromagnetic exchange interactions, these are strongly suppressed when considering dilute filling fractions. We argue that, instead, a small concentration of doped electrons leads to the formation of spin polarons, inducing ferromagnetic order at experimentally relevant temperatures, consistent with recently observed ferromagnetic states in moiré TMD systems. We predict explicit signatures of polaron formation in the magnetization profile.
Innate lymphoid cells (ILCs) play key roles in host defense, barrier integrity, and homeostasis and mirror adaptive CD4+ T helper (Th) cell subtypes in both usage of effector molecules and ...transcription factors. To better understand the relationship between ILC subsets and their Th cell counterparts, we measured genome-wide chromatin accessibility. We find that chromatin in proximity to effector genes is selectively accessible in ILCs prior to high-level transcription upon activation. Accessibility of these regions is acquired in a stepwise manner during development and changes little after in vitro or in vivo activation. Conversely, dramatic chromatin remodeling occurs in naive CD4+ T cells during Th cell differentiation using a type-2-infection model. This alteration results in a substantial convergence of Th2 cells toward ILC2 regulomes. Our data indicate extensive sharing of regulatory circuitry across the innate and adaptive compartments of the immune system, in spite of their divergent developing pathways.
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•Prototypical ILC subsets show distinctive regulomes•Regulatory elements of ILC effector genes are poised prior to activation•Regulomes of ILC subsets diverge early at precursor stages•Regulomes of innate and adaptive cells converge upon infection
Innate lymphoid cells and adaptive T helper cells become specialized cytokine-producing cells by distinct, but converging, routes.
How the immune system adapts to malnutrition to sustain immunity at barrier surfaces, such as the intestine, remains unclear. Vitamin A deficiency is one of the most common micronutrient deficiencies ...and is associated with profound defects in adaptive immunity. Here, we found that type 3 innate lymphoid cells (ILC3s) are severely diminished in vitamin A–deficient settings, which results in compromised immunity to acute bacterial infection. However, vitamin A deprivation paradoxically resulted in dramatic expansion of interleukin-13 (IL-13)–producing ILC2s and resistance to nematode infection in mice, which revealed that ILCs are primary sensors of dietary stress. Further, these data indicate that, during malnutrition, a switch to innate type 2 immunity may represent a powerful adaptation of the immune system to promote host survival in the face of ongoing barrier challenges.
We study transitions between topological phases featuring emergent fractionalized excitations in two-dimensional models for Mott insulators with spin and orbital degrees of freedom. The models ...realize fermionic quantum critical points in fractionalized Gross-Neveu* universality classes in (2+1) dimensions. They are characterized by the same set of critical exponents as their ordinary Gross-Neveu counterparts, but feature a different energy spectrum, reflecting the nontrivial topology of the adjacent phases. We exemplify this in a square-lattice model, for which an exact mapping to a t-V model of spinless fermions allows us to make use of large-scale numerical results, as well as in a honeycomb-lattice model, for which we employ ε-expansion and large-N methods to estimate the critical behavior. Our results are potentially relevant for Mott insulators with d^{1} electronic configurations and strong spin-orbit coupling, or for twisted bilayer structures of Kitaev materials.
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