Myeloid-derived suppressor cell, arginase-1, IL-17 and cl-CD95L: an explosive cocktail in lupus?

International audienceComment on: Wu H, Zhen Y, Ma Z, et al. Arginase-1-dependent promotion of TH17 differentiation and disease progression by MDSCs in systemic lupus erythematosus. Sci Transl Med 2016;8:331ra40

Ariel - Volume 1 Number 3

Copyright 1969 Arie

Dark halo baryons not in ancient halo white dwarfs

Having ruled out the possibility that stellar objects are the main contributor of the dark matter embedding galaxies, microlensing experiments cannot exclude the hypothesis that a significant fraction of the Milky Way dark halo might be made of MACHOs with masses in the range 0.5-0.8 \msun. Ancient white dwarfs are generally considered the most plausible candidates for such MACHOs. We report the results of a search for such white dwarfs in a proper motion survey covering a 0.16 sqd field at three epochs at high galactic latitude, and 0.938 sqd at two epochs at intermediate galactic latitude (VIRMOS survey), using the CFH telescope. Both surveys are complete to I = 23, with detection efficiency fading to 0 at I = 24.2. Proper motion data are suitable to separate unambiguously halo white dwarfs identified by belonging to a non rotating system. No candidates were found within the colour-magnitude-proper motion volume where such objects can be safely discriminated from any standard population as well as from possible artefacts. In the same volume, we estimate the maximum white dwarf halo fraction compatible with this observation at different significance levels if the halo is at least 14 gigayears old and under different ad hoc initial mass functions. Our data alone rules out a halo fraction greater than 14% at 95% confidence level. Combined with two previous investigations exploring comparable volumes pushes the limit below 4 % (95% confidence level) or below 1.3% (64% confidence), this implies that if baryonic dark matter is present in galaxy halos, it is not, or it is only marginally in the form of faint hydrogen white dwarfs.Comment: accepted in Astronomy and Astrophysics (19-05-2004

Toxoplasma gondii peroxiredoxin promotes altered macrophage function, caspase-1-dependent IL-1β secretion enhances parasite replication

Alternatively activated macrophages (AAM) are a key feature Th2 immunity and have been associated with a variety of roles during helminth infection. The role this cell subset plays in protzoan infection remain relatively unexplored, herein we describe the effects of a redox enzyme (rTgPrx) derived from Toxoplasma gondii on murine macrophage phenotype in vitro. RTgPrx has been previously associated with the maintainence of parasite oxidative balance. Here our experiments show that rTgPrx promotes AAM as indicated by high arginase-1 (arg-1), YM1 and FIZZ expression via both signal transducer and activator of transcription (STAT)6-dependent and -independent mechanisms. Additionally rTgPrx treatment reduced caspase-1 activity and IL-1β secretion, while simultaneously increasing IL-10 release. Furthermore the in vitro replication of T. gondii (RH strain) was enhanced when macrophages were treated with rTgPrx. This is in contrast with the previously described effects of a Plasmodium berghei ANKA 2-cys-peroxiredoxin that promotes pro-inflammatory cytokine production. These results highlight the role of T. gondii derived redox enzymes as important immune modulators and potentially indicate a role for AAM in modulating immunopathology and promoting parasite replication during T. gondii infection

Evasion of Host Immunity During Fasciola hepatica Infection.

Fasciola hepatica, the common liver fluke, causes infection of livestock throughout temperate regions of the globe. This helminth parasite has an indirect lifecycle, relying on the presence of the mud snail to complete its transition from egg to definitive host (Beesley et al., Transbound Emerg Dis 65:199-216, 2017). Within the definitive host, the parasite excysts in the intestine forming a newly excysted juvenile (NEJ) and migrates via the peritoneal cavity to the liver. Disease resulting from infection can be acute or chronic depending on the host and the number of parasites present. Sheep may succumb to a fatal acute infection if the challenge of metacercariae is great enough. However, in cattle chronic disease is the most likely outcome with parasites surviving for long periods of time. Annual losses are estimated to be in the region of US$ 2000 million to the agricultural industry (Beesley et al., Transbound Emerg Dis 65:199-216, 2017). Management of the disease depends heavily on chemotherapy with triclabendazole being the drug of choice, consistent use for over 20 years has resulted in drug-resistant strains emerging worldwide (Beesley et al., Int J Parasitol 47:11-20, 2017). A more sustainable approach to control would be through vaccination and indeed a lead candidate has been identified, cathepsin L1. Despite these promising results the parasite continues to confound our own and host efforts to generate long-lasting and effective immunity. In this brief review we focus our attention on those mechanisms that the parasite utilises to circumvent the innate based defense mechanisms within the host

Does the Milky Way have a Maximal Disk?

The Milky Way is often considered to be the best example of a spiral for which the dark matter not only dominates the outer kinematics, but also plays a major dynamical role in the inner galaxy: the Galactic disk is therefore said to be ``sub-maximal.'' This conclusion is important to the understanding of the evolution of galaxies and the viability of particular dark matter models. The Galactic evidence rests on a number of structural and kinematic measurements, many of which have recently been revised. The new constraints indicate not only that the Galaxy is a more typical member of its class (Sb-Sc spirals) than previously thought, but also require a re-examination of the question of whether or not the Milky Way disk is maximal. By applying to the Milky Way the same definition of ``maximal disk'' that is applied to external galaxies, it is shown that the new observational constraints are consistent with a Galactic maximal disk of reasonable $M/L$. In particular, the local disk column can be substantially less than the oft-quoted required \Sigma_{\odot} \approx 100 \msolar pc^{-2} - as low as 40 \msolar pc^{-2} in the extreme case - and still be maximal, in the sense that the dark halo provides negligible rotation support in the inner Galaxy. This result has possible implications for any conclusion that rests on assumptions about the potentials of the Galactic disk or dark halo, and in particular for the interpretation of microlensing results along both LMC and bulge lines of sight.Comment: Accepted for publication in The Astrophysical Journal. 23 Latex-generated pages, one (new) table, three figures (two new). A few additions to the bibliography, an expanded discussion, and slight quantitative changes, none of which affect the conclusion

TGF-? superfamily members from the helminth Fasciola hepatica show intrinsic effects on viability and development

© 2015 Japa et al.; licensee BioMed Central. The helminth Fasciola hepatica causes fasciolosis throughout the world, a major disease of livestock and an emerging zoonotic disease in humans. Sustainable control mechanisms such as vaccination are urgently required. To discover potential vaccine targets we undertook a genome screen to identify members of the transforming growth factor (TGF) family of proteins. Herein we describe the discovery of three ligands belonging to this superfamily and the cloning and characterisation of an activin/TGF like molecule we term FhTLM. FhTLM has a limited expression pattern both temporally across the parasite stages but also spatially within the worm. Furthermore, a recombinant form of this protein is able to enhance the rate (or magnitude) of multiple developmental processes of the parasite indicating a conserved role for this protein superfamily in the developmental biology of a major trematode parasite. Our study demonstrates for the first time the existence of this protein superfamily within F. hepatica and assigns a function to one of the three identified ligands. Moreover further exploration of this superfamily may yield future targets for diagnostic or vaccination purposes due to its stage restricted expression and functional role

Ariel - Volume 2 Number 3

Editors Delvyn C. Case, Jr. Paul M. Fernhoff News Editors Richard Bonanno Daniel B. Gould Robin A. Edwards Lay-Out Editor Carol Dolinskas Sports Editor James J. Nocon Contributing Editors Michael J. Blecker Lin Sey Edwards Jack Guralnik W. Cherry Light Features Editor Steven A. Ager Donald A. Bergman Stephen P. Flynn Business Manager Nick Greg

An inverse method to interpret colour-magnitude diagrams

An inverse method is developed to determine the star formation history, the age-metallicity relation, and the IMF slope from a colour-magnitude diagram. The method is applied to the Hipparcos HR diagram. We found that the thin disk of our Galaxy shows a peak of stellar formation 1.6 Gyr ago. The stars close to the Sun have a solar metallicity and a mean IMF index equal to 3.2. However, the model and the evolutionary tracks do not correctly reproduce the horizontal giant branch.Comment: 14 pages, 11 figures. To be published in Astronomy & Astrophysic

IL-17 and IL-22 elicited by a DNA vaccine encoding ROP13 associated with protection against Toxoplasma gondii in BALB/c mice.

Toxoplasma gondii, an intracellular parasitic protozoan, is capable of infecting man and all warm-blooded animals. Cell-mediated immunity is vital in mounting protective responses against T. gondii infection. Recent studies have shown that T-helper (Th) 17 responses may play a key role in parasite control. In this current study, we constructed a DNA vaccine encoding T. gondii ROP13 in a pcDNA vector. Groups of BALB/c mice were immunized intramuscularly with pcROP13 or controls and challenged with the RH strain of T. gondii. The results showed that immunization with pcROP13 could elicit an antibody response against T. gondii. The expression of the canonical Th17 cytokines, interleukin (IL)-17 and IL-22, were significantly increased after immunization with pcROP13 compared with control groups ( p < 0.05). Furthermore, vaccination resulted in a significant decrease in parasite load ( p < 0.05). The induction of Th17 related cytokines, using a ROP13 DNA vaccine, against T. gondii should be considered as a potential vaccine approach for the control of toxoplasmosis