Most bacteria naturally release spherical lipid-bilayered extracellular vesicles (EVs) containing proteins, nucleic acids, and virulence-related molecules, thus contributing to diverse biological ...functions including transport of virulence factors. The group A streptococcus,
(GAS), a major human pathogen, also releases EVs; however, it remains unclear how GAS EVs interact physiologically and pathologically with host cells, and what the differences are between invasive and non-invasive strains. The proteome profile in this study revealed that GAS EVs enclosed many virulence-related proteins such as streptolysin O and NAD-glycohydrolase, facilitating their pathogenicity, and invasive GAS EVs were more abundant than non-invasive counterparts. In terms of biological effects, invasive GAS EVs showed
-dependent cytotoxic activity and the induction of cytokine expression, contributing to GAS pathogenicity directly. Although non-invasive GAS EVs did not show cytotoxic activity, they may be utilized as a means to prevent antibacterial mechanisms such as autophagy, leading to enhancement of their own survival in the intracellular environment after the infection. These results suggest that invasive and non-invasive GAS EVs play different roles in GAS infection strategy and pathogenicity. Our findings also indicate that EVs could be a key factor for GAS pathogenicity in GAS-host interactions.
Adult T-cell leukemia/leukemia (ATLL) is an aggressive peripheral T-cell malignancy, caused by infection with the human T-cell leukemia virus type 1 (HTLV-1). We have recently shown that cell ...adhesion molecule 1 (CADM1), a member of the immunoglobulin superfamily, is specifically and consistently overexpressed in ATLL cells, and functions as a novel cell surface marker. In this study, we first show that a soluble form of CADM1 (sCADM1) is secreted from ATLL cells by mainly alternative splicing. After developing the Alpha linked immunosorbent assay (AlphaLISA) for sCADM1, we showed that plasma sCADM1 concentrations gradually increased during disease progression from indolent to aggressive ATLL. Although other known biomarkers of tumor burden such as soluble interleukin-2 receptor α (sIL-2Rα) also increased with sCADM1 during ATLL progression, multivariate statistical analysis of biomarkers revealed that only plasma sCADM1 was selected as a specific biomarker for aggressive ATLL, suggesting that plasma sCADM1 may be a potential risk factor for aggressive ATLL. In addition, plasma sCADM1 is a useful marker for monitoring response to chemotherapy as well as for predicting relapse of ATLL. Furthermore, the change in sCADM1 concentration between indolent and aggressive type ATLL was more prominent than the change in the percentage of CD4+CADM1+ ATLL cells. As plasma sCADM1 values fell within normal ranges in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients with higher levels of serum sIL-2Rα, a measurement of sCADM1 may become a useful tool to discriminate between ATLL and other inflammatory diseases, including HAM/TSP.
Parasites excrete and secrete a wide range of molecules that act as the primary interface with their hosts and play critical roles in establishing parasitism during different stages of infection. ...Strongyloides venezuelensis is a gastrointestinal parasite of rats that is widely used as a laboratory model and is known to produce both soluble and insoluble (adhesive) secretions during its parasitic stages. However, little is known about the constituents of these secretions.
Using mass spectrometry, we identified 436 proteins from the infective third-stage larvae (iL3s) and 196 proteins from the parasitic females of S. venezuelensis. The proteins that were secreted by the iL3s were enriched with peptidase activity, embryo development and the oxidation-reduction process, while those of the parasitic females were associated with glycolysis, DNA binding (histones) and other unknown functions. Trypsin inhibitor-like domain-containing proteins were identified as the main component of the adhesive secretion from parasitic females. An absence of secretion signals in many of the proteins indicated that they are secreted via non-classical secretion pathways.
We found that S. venezuelensis secretes a wide range of proteins to establish parasitism. This includes proteins that have previously been identified as being involved in parasitism in other helminths as well as proteins that are unique to this species. These findings provide insights into the molecular mechanisms underlying Strongyloides parasitism.
The aim of this study was to clarify the mechanism of leucocytapheresis (LCAP) in patients with RA.
Protein profiles of blood samples from two patients with RA obtained via LCAP column inlet and ...outlet lines were analysed by two-dimensional fluorescence difference gel electrophoresis and mass spectrometry. The lactoferrin (LTF) levels of peripheral and circulating blood samples from seven patients obtained via the LCAP column blood circuit were then determined by ELISA. Peripheral blood samples from 14 patients with RA were exposed to unwoven polyester fibre filters and the LTF level was determined. In addition, morphological changes in neutrophils after exposure to the filter were examined by optical microscopy, electronic microscopy and LTF immunostaining.
LTF levels were increased in both samples from the LCAP column outlet and peripheral blood at the end of LCAP treatment. Furthermore, peripheral blood samples exposed to the filter revealed a decreased number of neutrophils and an increased level of LTF. Morphological analysis of the exposed neutrophils showed vacuolization of the cytoplasm and degranulation of LTF-positive granules. These data suggest that LTF stored in the granules of neutrophils is released from the neutrophils caught in the LCAP column.
Because LTF has been reported to have multiple anti-inflammatory properties, increased levels of LTF may contribute to the clinical effect of LCAP in patients with RA.
Retinal degeneration involves neuroinflammation, and pro-inflammatory cytokines/chemokines are markedly increased in the eyes of patients with retinitis pigmentosa (RP). In this study, we ...investigated the changes of serum cytokines/chemokines in RP, and their relationships with visual parameters.
Forty-five consecutive patients with typical RP aged 20 to -39 years and 28 age-matched and gender-matched controls were included. Fifteen cytokines (interleukin IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, 1L-15, IL-17, IL-23, interferon IFN-γ, and tumor necrosis factor TNF-α, TNF-β) and 9 chemokines (eotaxin, growth-related oncogene GRO-α, I-309, IL-8, IFN-γ-inducible protein IP-10, monocyte chemotactic protein MCP-1, MCP-2, regulated activation normal T-cell expressed and secreted RANTES, and thymus and activated regulated chemokine TARC) in the serum were simultaneously measured by a multiplexed immunoarray (Q-Plex). Relationships between these cytokines/chemokines and indices of central vision, such as visual acuity (VA), the values of static perimetry tests (Humphrey Field analyzer, the central 10-2 program), and optical coherence tomography measures were analyzed in the patients with RP.
Among the 15 cytokines and 9 chemokines, serum IL-8 and RANTES levels were significantly increased in patients with RP compared with controls (IL-8: P < 0.0001; RANTES: P < 0.0001). Among the elevated cytokines/chemokines, the levels of IL-8 were negatively correlated with VA (ρ = 0.3596 and P = 0.0165), and the average retinal sensitivity of four central points (ρ = -0.3691 and P = 0.0291), and 12 central points (ρ = -0.3491 and P = 0.0398), as well as the central subfield thickness (ρ = -0.3961 and P = 0.0094), and ellipsoid zone width (ρ = -0.3841 and P = 0.0120).
Peripheral inflammatory response may be activated and serum IL-8 levels are associated with central vision in patients with RP.
Retinitis pigmentosa (RP) is an intractable inherited disease that primarily affects the rods through gene mutations followed by secondary cone degeneration. This cone-related dysfunction can lead to ...impairment of daily life activities, and ultimately blindness in patients with RP. Paradoxically, microglial neuroinflammation contributes to both protection against and progression of RP, but it is unclear which population(s) - tissue-resident microglia and/or peripheral monocyte-derived macrophages (mφ) - are implicated in the progression of the disease. Here we show that circulating blood inflammatory monocytes (IMo) are key effector cells that mediate cone cell death in RP. Attenuation of IMo and peripherally engrafted mφ by
deficiency or immune modulation via intravenous nano-particle treatment suppressed cone cell death in rd10 mice, an animal model of RP. In contrast, the depletion of resident microglia by a colony-stimulating factor 1 receptor inhibitor exacerbated cone cell death in the same model. In human patients with RP, IMo was increased and correlated with disease progression. These results suggest that peripheral IMo is a potential target to delay cone cell death and prevent blindness in RP.
The objective of this study is to identify the properties and responsible compounds for the aromatic roast odor (retort beef aroma) that commonly occurs in canned beef products and could contribute ...to their palatability. The optimal temperature for generating retort beef aroma was 121°C. An untrained panel evaluated both uncured corned beef and canned yamato‐ni beef and found that they had an aroma that was significantly (P < 0.01) similar to the odor of 121°C‐heated beef than 100°C‐heated beef. The panel also noted that the aroma of 121°C‐heated beef tended to be (P < 0.1) preferable than that of 100°C‐heated beef. These results suggest that retort beef aroma is one constituent of palatability in canned beef. GC‐MS (gas chromatography‐mass spectrometry) analysis of the volatile fraction obtained from 100°C‐ and 121°C‐heated beef showed that the amounts of pyrazine, 2‐methylpyrazine and diacetyl were higher in the 121°C‐heated beef than in the 100°C‐heated beef. GC‐sniffing revealed that the odor quality of pyrazines was similar to that of retort beef aroma. Therefore, pyrazines were suggested to be a candidate responsible for the retort beef aroma. Analysis of commercial uncured corned beef and cured corned beef confirmed the presence of pyrazine, 2‐methylpyrazine and 2,6‐dimethylpyrazine.
PDF
