Phylogenetic Analysis Indicates That Evasin-Like Proteins of Ixodid Ticks Fall Into Three Distinct Classes

Chemokines are structurally related proteins that activate leucocyte migration in response to injury or infection. Tick saliva contains chemokine-binding proteins or evasins which likely neutralize host chemokine function and inflammation. Biochemical characterisation of 50 evasins from Ixodes, Amblyomma and Rhipicephalus shows that they fall into two functional classes, A and B, with exclusive binding to either CC- or CXC- chemokines, respectively. Class A evasins, EVA1 and EVA4 have a four-disulfide-bonded core, whereas the class B evasin EVA3 has a three-disulfide-bonded “knottin” structure. All 29 class B evasins have six cysteine residues conserved with EVA3, arrangement of which defines a Cys6-motif. Nineteen of 21 class A evasins have eight cysteine residues conserved with EVA1/EVA4, the arrangement of which defines a Cys8-motif. Two class A evasins from Ixodes (IRI01, IHO01) have less than eight cysteines. Many evasin-like proteins have been identified in tick salivary transcriptomes, but their phylogenetic relationship with respect to biochemically characterized evasins is not clear. Here, using BLAST searches of tick transcriptomes with biochemically characterized evasins, we identify 292 class A and 157 class B evasins and evasin-like proteins from Prostriate (Ixodes), and Metastriate (Amblyomma, Dermacentor, Hyalomma, Rhipicephalus) ticks. Phylogenetic analysis shows that class A evasins/evasin-like proteins segregate into two classes, A1 and A2. Class A1 members are exclusive to Metastriate ticks and typically have a Cys8-motif and include EVA1 and EVA4. Class A2 members are exclusive to Prostriate ticks, lack the Cys8-motif, and include IHO01 and IRI01. Class B evasins/evasin-like proteins are present in both Prostriate and Metastriate lineages, typically have a Cys6-motif, and include EVA3. Most evasins/evasin-like proteins in Metastriate ticks belong to class A1, whereas in Prostriate species they are predominantly class B. In keeping with this, the majority of biochemically characterized Metastriate evasins bind CC-chemokines, whereas the majority of Prostriate evasins bind CXC-chemokines. While the origin of the structurally dissimilar classes A1 and A2 is yet unresolved, these results suggest that class B evasin-like proteins arose before the divergence of Prostriate and Metastriate lineages and likely functioned to neutralize CXC-chemokines and support blood feeding.

The Involvement of CXC Motif Chemokine Ligand 10 (CXCL10) and Its Related Chemokines in the Pathogenesis of Coronary Artery Disease and in the COVID-19 Vaccination: A Narrative Review

Coronary artery disease (CAD) and coronary heart disease (CHD) constitute two of the leading causes of death in Europe, USA and the rest of the world. According to the latest reports of the Iranian National Health Ministry, CAD is the main cause of death in Iranian patients with an age over 35 years despite a significant reduction in mortality due to early interventional treatments in the context of an acute coronary syndrome (ACS). Inflammation plays a fundamental role in coronary atherogenesis, atherosclerotic plaque formation, acute coronary thrombosis and CAD establishment. Chemokines are well-recognized mediators of inflammation involved in several bio-functions such as leucocyte migration in response to inflammatory signals and oxidative vascular injury. Different chemokines serve as chemo-attractants for a wide variety of cell types including immune cells. CXC motif chemokine ligand 10 (CXCL10), also known as interferon gamma-induced protein 10 (IP-10/CXLC10), is a chemokine with inflammatory features whereas CXC chemokine receptor 3 (CXCR3) serves as a shared receptor for CXCL9, 10 and 11. These chemokines mediate immune responses through the activation and recruitment of leukocytes, eosinophils, monocytes and natural killer (NK) cells. CXCL10, interleukin (IL-15) and interferon (IFN-g) are increased after a COVID-19 vaccination with a BNT162b2 mRNA (Pfizer/BioNTech) vaccine and are enriched by tumor necrosis factor alpha (TNF-α) and IL-6 after the second vaccination. The aim of the present study is the presentation of the elucidation of the crucial role of CXCL10 in the patho-physiology and pathogenesis of CAD and in identifying markers associated with the vaccination resulting in antibody development.

Antinociceptive and anti-inflammatory effect of Lippia pedunculosa Hayek essential oil and its β-cyclodextrin inclusion complex

Lippia pedunculosa Hayek (EOLp) presents tripanocid and amebicid effects. However essential oil needs to be further studied in experimental models of analgesia and inflammation once the prevalence of pain in the population generates great suffering and disability and the drugs most often used have undesirable side effects. We also evaluated whether the inclusion complex formulation EOLp/β-cyclodextrin (β-CD) was able to improve the antinociceptive activity of the EOLp alone. Data were evaluated by analysis of variance (ANOVA), followed by Tukey’s test. Differences were considered significant if p<0.05. EOLp presented better antinociceptive effect when compared to the EOLp/β-CD inclusion complex. Thus, cyclodextrins appear not to be efficient for essential oils with peroxide substances. However, in peritonitis, EOLp reduced total leucocyte migration and IL-1β levels in the peritoneal fluid, which confirmed its anti-inflammatory effect. The observed effects suggest that EOLp is the best promising option for the treatment of inflammation and pain-related disorders.

Recovery of monocyte exhaustion is associated with resolution of lung injury in COVID-19 convalescence

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulting in the clinical syndrome COVID-19 is associated with an exaggerated immune response and monocyte infiltrates in the lungs and other peripheral tissues. It is now increasingly recognised that chronic morbidity persists in some patients. We recently demonstrated profound alterations of monocytes in hospitalised COVID-19 patients. It is currently unclear whether these abnormalities resolve or progress following patient discharge. We show here that blood monocytes in convalescent patients at their 12 week follow up, have a greater propensity to produce pro-inflammatory cytokines TNFα and IL-6, which was consistently higher in patients with resolution of lung injury as indicated by a normal chest X-ray and no shortness of breath (a key symptom of lung injury). Furthermore, monocytes from convalescent patients also displayed enhanced levels of molecules involved in leucocyte migration, including chemokine receptor CXCR6, adhesion molecule CD31/PECAM and integrins VLA-4 and LFA-1. Expression of migration molecules on monocytes was also consistently higher in convalescent patients with a normal chest X-ray. These data suggest persistent changes in innate immune function following recovery from COVID-19 and indicate that immune modulating therapies targeting monocytes and leucocyte migration may be useful in recovering COVID-19 patients with persistent symptoms.

Antioxidant Vitamins Are Correlated with Different Aspects of Phagocytic Processes in Healthy Nigerians: Benefits As Supplements During Antimicrobial Treatment

Background: Antioxidant vitamins are important for the immune system to function efficiently through several mechanisms. However, according to several previous studies, individual step of leucocyte phagocytosis is not correlated with different antioxidant vitamins. Methods: This study included 50 healthy Nigerians whose cellular phagocytic mechanism such as percentage leucocyte migration (%LM) and intracellular killing (%Nitroblue Tetrazolium Test) were determined by microscopy, neutrophil chemokines [plasma interleukin 8 (IL-8)] was determined using ELISA, and respiratory burst indices [plasma catalase (CAT), superoxide dismutase (SOD), myeloperoxidase (MPO), hydrogen peroxide (H2O2), and nitric oxide (NO)] were determined by spectrophotometry. While the plasma antioxidant vitamins (Vitamins A, C, and E) were determined using HPLC, the phagocytic indices, chemokines, and respiratory burst indices were correlated with plasma antioxidant vitamins using Spearman’s Correlation analysis at α0.05. Results: The results show that although among the healthy Nigerian adults, vitamin C was significantly and positively correlated with %NBT, it was negatively correlated with CAT activity. Vitamin A showed a significantly positive correlation with SOD while Vitamin E showed a significantly negative correlation with MPO. Conclusions: These findings suggest that antioxidant vitamins affect different stages of phagocytosis. It is advisable to use a combination of antioxidant vitamins as supplements with recommended treatment strategies against intracellular micro-organisms or inflammatory diseases. Keywords: Antioxidants, Intracellular microbial killing, Vitamins

Eleusine indica Linn, Baertin (Poaceae) Ethanol Leaf Extract and Its Ethyl Acetate Fraction Display Potential Anti-inflammatory Activities

Objective: Inflammation is the underlying cause of most of the chronic diseases that occur with aging. Although many drugs are available for the management of inflammatory disorders and their symptoms, most of these drugs possess serious adverse effects that limit their usefulness. This has encouraged the unending search for potent anti-inflammatory drugs from plant sources as alternatives to conventional drug treatment of inflammation. This study investigated the anti-inflammatory activities of the ethanol leaf extract of E. indica and the ethylacetate fraction in rodents. Materials and Methods: The leaves were extracted with ethanol by cold maceration and the extract was fractionated with n-hexane, ethylacetate, butanol and water. The oral acute toxicity (LD50) of the extract and the phytochemical constituents of the extract and the fractions were determined. The anti-inflammatory activities of the ethanol extract (EE) and ethylacetate fraction (ETF) and their possible mechanisms of actions were investigated. Results: The oral LD50 of the extract was above 5000 mg/kg. Both the EE and ETF displayed dose-dependent inhibition of the rat paw edema, with ETF producing between 48-54% edema inhibition. Xylene-induced topical edema was significantly (p < 0.05) reduced by both the EE and ETF, with ETF causing between 48 and 65% inhibition. The EE and ETF preserved the integrity of gastric mucosa. Their average ulcer index (1.37±0.02) was significantly lower than that of indomethacin (5.20±0.23). Pre-treatment with the EE and ETF significantly (p < 0.05) reduced leucocyte migration, especially the neutrophils. Both heat- and hypotonicity-induced hemolysis of RBC membrane were remarkably inhibited. Conclusion: The mechanisms of the anti-inflammatory activity may involve among others inhibition of leukocyte migration and membrane stabilization.

MCP-1 produced by keratinocytes is associated with leucocyte recruitment during elicitation of nickel-induced occupational allergic contact dermatitis

To investigate the expression profile of monocyte chemoattractant peptide-1 (MCP-1) by keratinocytes after nickel exposure and to identify its role for leucocyte migration during nickel-induced occupational allergic contact dermatitis (OACD), 26 workers diagnosed with nickel-induced OACD were enrolled. Skin biopsies from the positive nickel-challenged sites at different time points were assessed by immunohistochemistry (IHC) for MCP-1, CD68, CD45RO, and in situ hybridization (ISH) for MCP-1, using chronic periumbilical dermititis as controls. The expressions of MCP-1 in HaCaT cell culture after nickel treatment were quantified by enzyme-linked immunosorbent assay. The results showed that at positive nickel-challenged sites, strong expressions of MCP-1, both messenger RNA (mRNA) and protein, were detected in the basal keratinocytes during the early phase (24–48 h after nickel application), paralleled by the recruitment of CD68+ and CD45RO+ cells to the skin compartments. The expressions of MCP-1 declined gradually in the late phase (72–96 h after nickel application). Treatment with nickel sulfate at noncytotoxic concentrations (0.01–100 µM) induced a concentration-related elevation of MCP-1 expression by HaCaT cells compared to the untreated cells. The data indicated that a temporal expression pattern of MCP-1 produced by keratinocytes after nickel exposure was involved in the complex process of mononuclear cell infiltration during elicitation of nickel-induced OACD. Targeting MCP-1 might be a potential therapeutic strategy for OACD.

Positive Correlation between IP-10 and IFN-γLevels in Rhesus Monkeys(Macaca mulatta)with Either Naturally Acquired or Experimental Infection ofMycobacterium tuberculosis

Numerous studies identify that IP-10 and IFN-γare involved in leucocyte migration and activation and regarded as promising surrogate biomarkers in human and bovine tuberculosis infection, but there is lack of evidence for IP-10 in nonhuman primates. In this study, we directly determined IP-10 and IFN-γlevels in plasma from 30 healthy monkeys, 30 monkeys with naturally acquired tuberculosis, 4 monkeys experimentally infected with tuberculosis, and PPD stimulated whole blood of 14 monkeys with naturally acquired tuberculosis by ELISA. Higher plasma levels of IP-10 and IFN-γwere observed in natural tuberculosis monkeys than in healthy controls. The dynamic changes of plasma IP-10 and IFN-γin experimental infections showed consistent representation of a transient increase during the infection period. After PPD stimulation, release of IP-10 and IFN-γis significantly induced in natural tuberculosis monkeys, but the stimulation index of IP-10 was significantly lower than IFN-γ. Further analysis showed that positive correlation between IP-10 and IFN-γexisted in healthy and tuberculosis monkeys. Our findings support plasma IP-10 and IFN-γas biomarkers for monitoring ongoing inflammation of nonhuman primate tuberculosis, and IFN-γis a more valuable diagnostic biomarker.