Major Surface Antigens in Zoonotic Babesia

Human babesiosis results from a combination of tick tropism for humans, susceptibility of a host to sustain Babesia development, and contact with infected ticks. Climate modifications and increasing diagnostics have led to an expanded number of Babesia species responsible for human babesiosis, although, to date, most cases have been attributed to B. microti and B. divergens. These two species have been extensively studied, and in this review, we mostly focus on the antigens involved in host–parasite interactions. We present features of the major antigens, so-called Bd37 in B. divergens and BmSA1/GPI12 in B. microti, and highlight the roles of these antigens in both host cell invasion and immune response. A comparison of these antigens with the major antigens found in some other Apicomplexa species emphasizes the importance of glycosylphosphatidylinositol-anchored proteins in host–parasite relationships. GPI-anchor cleavage, which is a property of such antigens, leads to soluble and membrane-bound forms of these proteins, with potentially differential recognition by the host immune system. This mechanism is discussed as the structural basis for the protein-embedded immune escape mechanism. In conclusion, the potential consequences of such a mechanism on the management of both human and animal babesiosis is examined.

Non-respiratory functions of lungs in experimental intracerebral hemorage during fingolimod injection

Introduction. Intracerebral hemorrhage (ICH) is frequently accompanied by respiratory system complications. One of the correction method of post stroke complications is administration of immunosuppressive drug fingolimod. Theobjective of the study is to investigate non-respiratory lung functions in experimental ICH during fingolimod treatment. Materials and methods. Animals were divided into 3 groups: group 1 with ICH, group 2 with ICH receiving fingolimod and group 3 as reference group. Intracranial hemorrhage was modelled by 160 μl autologic blood injection into lateral brain ventricle (P=0.6; D=1.5; V=3.5). Fingolimod (FTY 720, «Sigma») was administered within 1 hour after ICH (intraabdominal, 1 mg/kg). Biochemistry and functional parameters of the lung surfactant in animals were studied. Phospholipids fractions spectrum was assessed by thin-layer chromatography, superficial surfactant activity by Wilhelmi method. Parameters of water metabolism, pulmonary blood filling were studied by gravimetric method. Level of blood nitric oxide was estimated by amount of nitrates and nitrites stable terminal metabolites. Results. We revealed that experimental ICH causes a decrease of alveolar stability index by 9 %, decrease of total alveolar phospholipids content by 25 % and change of its fraction composition, i.e. decrease of major surface active fraction (phosphatidylcholine) by 68 %, increase of phosphatidic acid amount by 151 % and increase of lisophosphatidylcholine by 163 %. Besides that, experimental ICH is followed by lung edema on the lung blood filling background and increase of blood NO. Fingolimod administration does not affect surfactant surface activity but totally corrects water balance, lung blood filling and blood NO content.

Current State of Carbohydrate Recognition and C-Type Lectin Receptors in Pneumocystis Innate Immunity

Pneumocystis jirovecii is one of the most common fungal pathogens in immunocompromised individuals. Pneumocystis jirovecii pneumonia (PJP) causes a significant host immune response that is driven greatly by the organism’s cell wall components including β-glucans and major surface glycoprotein (Msg). These ligands interact with a number of C-type lectin receptors (CLRs) leading to downstream activation of proinflammatory signaling pathways. This minireview provides a brief overview summarizing known CLR/Pneumocystis interactions.

Additional C-type lectin receptors mediate interactions with Pneumocystis organisms and major surface glycoprotein

Introduction. Pathogen-associated molecular patterns’ (PAMPs) are microbial signatures that are recognized by host myeloid C-type lectin receptors (CLRs). These CLRs interact with micro-organisms via their carbohydrate recognition domains (CRDs) and engage signalling pathways within the cell resulting in pro-inflammatory and microbicidal responses. Gap statement. In this article, we extend our laboratory study of additional CLRs that recognize fungal ligands against Pneumocystis murina and Pneumocystis carinii and their purified major surface glycoproteins (Msgs). Aim. To study the potential of newly synthesized hFc-CLR fusions on binding to Pneumocystis and its Msg. Methods. A library of new synthesized hFc-CLR fusions was screened against Pneumocystis murina and Pneumocystis carinii organisms and their purified major surface glycoproteins (Msgs) found on the respective fungi via modified ELISA. Immunofluorescence assay (IFA) was implemented and quantified to verify results. mRNA expression analysis by quantitative PCR (q-PCR) was employed to detect respective CLRs found to bind fungal organisms in the ELISA and determine their expression levels in the mouse immunosuppressed Pneumocystis pneumonia (PCP) model. Results. We detected a number of the CLR hFc-fusions displayed significant binding with P. murina and P. carinii organisms, and similarly to their respective Msgs. Significant organism and Msg binding was observed for CLR members C-type lectin domain family 12 member A (CLEC12A), Langerin, macrophage galactose-type lectin-1 (MGL-1), and specific intracellular adhesion molecule-3 grabbing non-integrin homologue-related 3 (SIGNR3). Immunofluorescence assay (IFA) with the respective CLR hFc-fusions against whole P. murina life forms corroborated these findings. Lastly, we surveyed the mRNA expression profiles of the respective CLRs tested above in the mouse immunosuppressed Pneumocystis pneumonia (PCP) model and determined that macrophage galactose type C-type lectin (Mgl-1), implicated in recognizing terminal N-acetylgalactosamine (GalNAc) found in the glycoproteins of microbial pathogens was significantly up-regulated during infection. Conclusion. The data herein add to the growing list of CLRs recognizing Pneumocystis and provide insights for further study of organism/host immune cell interactions.

First plasma exposure of a pre-damaged ITER-like plasma facing unit in the WEST tokamak: procedure for the PFU preparation and lessons learnt

The evaluation of the impact of plasma-facing components (PFCs) damage on subsequent plasma operation is an important issue for ITER. During the first phase of operation of WEST, a few ITER like divertor plasma-facing units (PFUs) have been installed on the lower divertor. One PFU was pre-damaged under electron beam gun thermal loading, before its installation in WEST, and the subsequent evolution of the damage was studied after the WEST plasma exposure. This paper presents the procedure followed to get the pre-damaged PFU. It consists in the characterization of the response of tungsten samples representative of WEST PFU under high heat flux (HHF) loading, the selection of damage (namely small cracks, crack network, crack network and W melt droplets). Finally, according to the WEST plasma loading conditions, the blocks with damage within the PFU and the position of the pre-damaged PFU on the WEST lower divertor are attributed. The first results obtained after an initial plasma exposure in WEST lead to assess, as expected with regard to the heat loading conditions, that no major surface aspect modification was found. This result emphasized the possibility to implement as pre-damage some small local droplets of melted tungsten in a high heat loaded zone for a future WEST experimental campaign.

Lipopolysaccharide of the Yersinia pseudotuberculosis Complex

Lipopolysaccharide (LPS), localized in the outer leaflet of the outer membrane, serves as the major surface component of the Gram-negative bacterial cell envelope responsible for the activation of the host’s innate immune system. Variations of the LPS structure utilized by Gram-negative bacteria promote survival by providing resistance to components of the innate immune system and preventing recognition by TLR4. This review summarizes studies of the biosynthesis of Yersinia pseudotuberculosis complex LPSs, and the roles of their structural components in molecular mechanisms of yersiniae pathogenesis and immunogenesis.

Stress Induces Release of Extracellular Vesicles by Trypanosoma cruzi Trypomastigotes

All extracellular forms of Trypanosoma cruzi, the causative agent of Chagas disease, release extracellular vesicles (EVs) containing major surface molecules of the parasite. EV release depends on several mechanisms (internal and external). However, most of the environmental conditions affecting this phenomenon are still unknown. In this work, we evaluated EV release under different stress conditions and their ability to be internalized by the parasites. In addition, we investigated whether the release conditions would affect their immunomodulatory properties in preactivated bone marrow-derived macrophages (BMDM). Sodium azide and methyl-cyclo-β-dextrin (CDB) reduced EV release, indicating that this phenomenon relies on membrane organization. EV release was increased at low temperatures (4°C) and acidic conditions (pH 5.0). Under this pH, trypomastigotes differentiated into amastigotes. EVs are rapidly liberated and reabsorbed by the trypomastigotes in a concentration-dependent manner. Nitrosative stress caused by sodium nitrite in acid medium or S-nitrosoglutathione also stimulated the secretion of EVs. EVs released under all stress conditions also maintained their proinflammatory activity and increased the expression of iNOS, Arg 1, IL-12, and IL-23 genes in IFN-γ and LPS preactivated BMDM. In conclusion, our results suggest a budding mechanism of release, dependent on the membrane structure and parasite integrity. Stress conditions did not affect functional properties of EVs during interaction with host cells. EV release variations under stress conditions may be a physiological response against environmental changes.