838 research outputs found
Wolbachia endosymbionts induce neutrophil extracellular trap formation in human onchocerciasis
The endosymbiotic bacteria, Wolbachia, induce neutrophilic responses to the human helminth pathogen Onchocerca volvulus. The formation of Neutrophil Extracellular Traps (NETs), has been implicated in anti-microbial defence, but has not been identified in human helminth infection. Here, we demonstrate NETs formation in human onchocerciasis. Extracellular NETs and neutrophils were visualised around O. volvulus in nodules excised from untreated patients but not in nodules from patients treated with the anti-Wolbachia drug, doxycycline. Whole Wolbachia or microspheres coated with a synthetic Wolbachia lipopeptide (WoLP) of the major nematode Wolbachia TLR2/6 ligand, peptidoglycan associated lipoprotein, induced NETosis in human neutrophils in vitro. TLR6 dependency of Wolbachia and WoLP NETosis was demonstrated using purified neutrophils from TLR6 deficient mice. Thus, we demonstrate for the first time that NETosis occurs during natural human helminth infection and demonstrate a mechanism of NETosis induction via Wolbachia endobacteria and direct ligation of Wolbachia lipoprotein by neutrophil TLR2/6
Glycoinositolphospholipids from Leishmania braziliensis and L. infantum: Modulation of Innate Immune System and Variations in Carbohydrate Structure
The essential role of the lipophosphoglycan (LPG) of Leishmania in innate immune response has been extensively reported. However, information about the role of the LPG-related glycoinositolphospholipids (GIPLs) is limited, especially with respect to the New World species of Leishmania. GIPLs are low molecular weight molecules covering the parasite surface and are similar to LPG in sharing a common lipid backbone and a glycan motif containing up to 7 sugars. Critical aspects of their structure and functions are still obscure in the interaction with the vertebrate host. In this study, we evaluated the role of those molecules in two medically important South American species Leishmania infantum and L. braziliensis, causative agents of visceral (VL) and cutaneous Leishmaniasis (CL), respectively. GIPLs derived from both species did not induce NO or TNF-α production by non-primed murine macrophages. Additionally, primed macrophages from mice (BALB/c, C57BL/6, TLR2−/− and TLR4−/−) exposed to GIPLs from both species, with exception to TNF-α, did not produce any of the cytokines analyzed (IL1-β, IL-2, IL-4, IL-5, IL-10, IL-12p40, IFN-γ) or p38 activation. GIPLs induced the production of TNF-α and NO by C57BL/6 mice, primarily via TLR4. Pre incubation of macrophages with GIPLs reduced significantly the amount of NO and IL-12 in the presence of IFN-γ or lipopolysaccharide (LPS), which was more pronounced with L. braziliensis GIPLs. This inhibition was reversed after PI-specific phospholipase C treatment. A structural analysis of the GIPLs showed that L. infantum has manose rich GIPLs, suggestive of type I and Hybrid GIPLs while L. braziliensis has galactose rich GIPLs, suggestive of Type II GIPLs. In conclusion, there are major differences in the structure and composition of GIPLs from L. braziliensis and L. infantum. Also, GIPLs are important inhibitory molecules during the interaction with macrophages
IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection
Funding: This work was funded by a Career Development Fellowship (1028634) and a project grant (GRNT1028641) awarded to AHa by the Australian National Health & Medical Research Council (NHMRC). IS was supported by The University of Queensland Centennial and IPRS Scholarships. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD
A transcriptomic snapshot of early molecular communication between Pasteuria penetrans and Meloidogyne incognita
© The Author(s). 2018Background: Southern root-knot nematode Meloidogyne incognita (Kofoid and White, 1919), Chitwood, 1949 is a key pest of agricultural crops. Pasteuria penetrans is a hyperparasitic bacterium capable of suppressing the nematode reproduction, and represents a typical coevolved pathogen-hyperparasite system. Attachment of Pasteuria endospores to the cuticle of second-stage nematode juveniles is the first and pivotal step in the bacterial infection. RNA-Seq was used to understand the early transcriptional response of the root-knot nematode at 8 h post Pasteuria endospore attachment. Results: A total of 52,485 transcripts were assembled from the high quality (HQ) reads, out of which 582 transcripts were found differentially expressed in the Pasteuria endospore encumbered J2 s, of which 229 were up-regulated and 353 were down-regulated. Pasteuria infection caused a suppression of the protein synthesis machinery of the nematode. Several of the differentially expressed transcripts were putatively involved in nematode innate immunity, signaling, stress responses, endospore attachment process and post-attachment behavioral modification of the juveniles. The expression profiles of fifteen selected transcripts were validated to be true by the qRT PCR. RNAi based silencing of transcripts coding for fructose bisphosphate aldolase and glucosyl transferase caused a reduction in endospore attachment as compared to the controls, whereas, silencing of aspartic protease and ubiquitin coding transcripts resulted in higher incidence of endospore attachment on the nematode cuticle. Conclusions: Here we provide evidence of an early transcriptional response by the nematode upon infection by Pasteuria prior to root invasion. We found that adhesion of Pasteuria endospores to the cuticle induced a down-regulated protein response in the nematode. In addition, we show that fructose bisphosphate aldolase, glucosyl transferase, aspartic protease and ubiquitin coding transcripts are involved in modulating the endospore attachment on the nematode cuticle. Our results add new and significant information to the existing knowledge on early molecular interaction between M. incognita and P. penetrans.Peer reviewedFinal Published versio
Cyclodextrin/cellulose hydrogel with gallic acid to prevent wound infection
Cyclodextrin-based hydrogels have been described as suitable for the controlled-release of bioactive molecules to be used as wound dressing. These materials have major advantages, since they gather the hydrogel properties (high degree of swelling and easy manipulation) and the encapsulation ability of cyclodextrins. β-cyclodextrin (β) or hydroxypropyl-β-cyclodextrin (HPβ) was cross-linked (1,4-butanediol diglycidyl ether) with hydroxypropyl methylcellulose under mild conditions. The hydrogels were chemically characterized by swelling degree, FTIR, DSC and contact angle. The gallic acid loading and release was also analysed, as well the antibacterial activity and cytotoxicity of the polymeric networks. The hydrogels obtained were firm and transparent, with good swelling ability. The gel-HPβ had a surface more hydrophilic when compared with the gel-β. Nevertheless, both hydrogels were capable to incorporate gallic acid and sustain the release for 48 h. The antibacterial activity of gallic acid was maintained after its adsorption within the polymeric matrix, as well as, gallic acid effect on fibroblast proliferation. Therefore, gel-β and gel-HPβ conjugated with gallic acid were shown to be a viable option for antibacterial wound dressing.The authors thank the FCT Strategic Projects PEst-OE/EQB/LA0023/2013, PEst-C/CTM/UI0264/2011, the Project "BioHealth-Biotechnology and Bioengineering approaches to improve health quality'', Ref. NORTE-07-0124-FEDER-000027, co-funded by the Programa Operacional Regional doNorte (ON.2-ONovoNorte), QREN, FEDER, and E. Pinho grant (SFRH/BD/62665/2009)
Phospholipids Trigger Cryptococcus neoformans Capsular Enlargement during Interactions with Amoebae and Macrophages
A remarkable aspect of the interaction of Cryptococcus
neoformans with mammalian hosts is a consistent increase in capsule
volume. Given that many aspects of the interaction of C.
neoformans with macrophages are also observed with amoebae, we
hypothesized that the capsule enlargement phenomenon also had a protozoan
parallel. Incubation of C. neoformans with Acanthamoeba
castellanii resulted in C. neoformans capsular
enlargement. The phenomenon required contact between fungal and protozoan cells
but did not require amoeba viability. Analysis of amoebae extracts showed that
the likely stimuli for capsule enlargement were protozoan polar lipids. Extracts
from macrophages and mammalian serum also triggered cryptococcal capsular
enlargement. C. neoformans capsule enlargement required
expression of fungal phospholipase B, but not phospholipase C. Purified
phospholipids, in particular, phosphatidylcholine, and derived molecules
triggered capsular enlargement with the subsequent formation of giant cells.
These results implicate phospholipids as a trigger for both C.
neoformans capsule enlargement in vivo and
exopolysaccharide production. The observation that the incubation of C.
neoformans with phospholipids led to the formation of giant cells
provides the means to generate these enigmatic cells in vitro.
Protozoan- or mammalian-derived polar lipids could represent a danger signal for
C. neoformans that triggers capsular enlargement as a
non-specific defense mechanism against potential predatory cells. Hence,
phospholipids are the first host-derived molecules identified to trigger
capsular enlargement. The parallels apparent in the capsular response of
C. neoformans to both amoebae and macrophages provide
additional support for the notion that certain aspects of cryptococcal virulence
emerged as a consequence of environmental interactions with other microorganisms
such as protists
Double Diffraction Dissociation at the Fermilab Tevatron Collider
We present results from a measurement of double diffraction dissociation in
collisions at the Fermilab Tevatron collider. The production cross
section for events with a central pseudorapidity gap of width
(overlapping ) is found to be [] at [630]
GeV. Our results are compared with previous measurements and with predictions
based on Regge theory and factorization.Comment: 10 pages, 4 figures, using RevTeX. Submitted to Physical Review
Letter
Blockade of the co-inhibitory molecule PD-1 unleashes ILC2-dependent antitumor immunity in melanoma.
Group 2 innate lymphoid cells (ILC2s) are essential to maintain tissue homeostasis. In cancer, ILC2s can harbor both pro-tumorigenic and anti-tumorigenic functions, but we know little about their underlying mechanisms or whether they could be clinically relevant or targeted to improve patient outcomes. Here, we found that high ILC2 infiltration in human melanoma was associated with a good clinical prognosis. ILC2s are critical producers of the cytokine granulocyte-macrophage colony-stimulating factor, which coordinates the recruitment and activation of eosinophils to enhance antitumor responses. Tumor-infiltrating ILC2s expressed programmed cell death protein-1, which limited their intratumoral accumulation, proliferation and antitumor effector functions. This inhibition could be overcome in vivo by combining interleukin-33-driven ILC2 activation with programmed cell death protein-1 blockade to significantly increase antitumor responses. Together, our results identified ILC2s as a critical immune cell type involved in melanoma immunity and revealed a potential synergistic approach to harness ILC2 function for antitumor immunotherapies
Study of decays to the final state and evidence for the decay
A study of decays is performed for the first time
using data corresponding to an integrated luminosity of 3.0
collected by the LHCb experiment in collisions at centre-of-mass energies
of and TeV. Evidence for the decay
is reported with a significance of 4.0 standard deviations, resulting in the
measurement of
to
be .
Here denotes a branching fraction while and
are the production cross-sections for and mesons.
An indication of weak annihilation is found for the region
, with a significance of
2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html,
link to supplemental material inserted in the reference
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