GRANULITISATION OF FRONTAL NAPPES IN THE KABYÈ MASSIF IN NORTHERN TOGO

The Kabyè Massif represents one of disseminated hills which marks the suture zone of the Panafrican Dahomeyides Belt in northen Togo. Coronitic structures were described in high-grade granulites composing the frontal nappes on the south-western edge of the massif. Granulitisation is investigated through petrofabric study of the frontal nappes rocks of Kabyè Massif. Two stages of granulitisation are revealed: the first one corresponds to the formation of granulites with an Opx + Pl + Cpx + Grt ± Qtz paragenesis ; the second one has a Cpx + Pl + Grt + Qtz ± Ilm mineral assemblage. The former corresponds to metamorphic recristallization of about medium-pressure to high-temperature conditions (P = 10 to 13 kbar and T = 900 with 1000°C). The latter, which developed coronitic structures, is interpretated as formed at an ultra-high-pressure and medium- to hightemperature conditions (P = 13 to 19 kbar and T = 850 to 900°C). These coronitic petro-fabrics define an anticlockwise P-T paths trajectories corresponding to the collision and the beginning of the nappes extraction during the Panafrican tectonics

GRANULITISATION OF FRONTAL NAPPES IN THE KABYÈ MASSIF IN NORTHERN TOGO

The Kabyè Massif represents one of disseminated hills which marks the suture zone of the Panafrican Dahomeyides Belt in northen Togo. Coronitic structures were described in high-grade granulites composing the frontal nappes on the south-western edge of the massif. Granulitisation is investigated through petrofabric study of the frontal nappes rocks of Kabyè Massif. Two stages of granulitisation are revealed: the first one corresponds to the formation of granulites with an Opx + Pl + Cpx + Grt ± Qtz paragenesis ; the second one has a Cpx + Pl + Grt + Qtz ± Ilm mineral assemblage. The former corresponds to metamorphic recristallization of about medium-pressure to high-temperature conditions (P = 10 to 13 kbar and T = 900 with 1000°C). The latter, which developed coronitic structures, is interpretated as formed at an ultra-high-pressure and medium- to hightemperature conditions (P = 13 to 19 kbar and T = 850 to 900°C). These coronitic petro-fabrics define an anticlockwise P-T paths trajectories corresponding to the collision and the beginning of the nappes extraction during the Panafrican tectonics

Interplay between foetal haemoglobin, micronutrients and oxidative stress biomarkers in sickle cell anaemia children

Foetal haemoglobin (HbF) has been speculated to have an impact on the quantity of micronutrients and the latter also have a role to play in oxidative stress (OS) in sickle cell anaemia (SCA). No previous study in Ghana has examined the interplay of these factors together among SCA children. This study compared the levels of OS biomarkers (8-hydroxy-deoxyguanosine [8-OHdG] total antioxidant capacity [TAC]) and micronutrients (zinc and copper), and their relationship with HbF in SCA and sickle cell negative, apparently healthy children. This case-control study recruited 58 SCA (out-patients [n = 42] and in-patients [n = 16]) children aged 1–14 years as cases and 62 sickle cell negative children as controls from the Sickle Cell Unit at the Eastern Regional Hospital, Ghana. The micronutrients were measured using the atomic absorption spectrophotometer (AAS) whereas OS biomarkers and HbF were assayed using enzyme-linked immunosorbent assay (ELISA). SCA out-patients had a significantly higher level of HbF compared to HbA patients (p = 0.035). SCA in-patients had significantly increased levels of zinc, but a reduced 8-OHdG than SCA out-patients compared to control group (p \u3c 0.05). HbF correlated significantly (r = 0.318, p \u3c 0.038) with zinc in SCA out-patients. Micronutrients are essential in maintaining the redox status in SCA out-patients and HbF can influence some micronutrients

Intranasal Administration of poly(I:C) and LPS in BALB/c Mice Induces Airway Hyperresponsiveness and Inflammation via Different Pathways

BACKGROUND: Bacterial and viral infections are known to promote airway hyperresponsiveness (AHR) in asthmatic patients. The mechanism behind this reaction is poorly understood, but pattern recognizing Toll-like receptors (TLRs) have recently been suggested to play a role. MATERIALS AND METHODS: To explore the relation between infection-induced airway inflammation and the development of AHR, poly(I:C) activating TLR3 and LPS triggering TLR4, were chosen to represent viral and bacterial induced interactions, respectively. Female BALB/c or MyD88-deficient C57BL/6 mice were treated intranasally with either poly(I:C), LPS or PBS (vehicle for the control group), once a day, during 4 consecutive days. RESULTS: When methacholine challenge was performed on day 5, BALB/c mice responded with an increase in airway resistance. The maximal resistance was higher in the poly(I:C) and LPS treated groups than among the controls, indicating development of AHR in response to repeated TLR activation. The proportion of lymphocytes in broncheoalveolar lavage fluid (BALF) increased after poly(I:C) treatment whereas LPS enhanced the amount of neutrophils. A similar cellular pattern was seen in lung tissue. Analysis of 21 inflammatory mediators in BALF revealed that the TLR response was receptor-specific. MyD88-deficient C57BL/6 mice responded to poly (I:C) with an influx of lymphocytes, whereas LPS caused no inflammation. CONCLUSION: In vivo activation of TLR3 and TLR4 in BALB/c mice both caused AHR in conjunction with a local inflammatory reaction. The AHR appeared to be identical regardless of which TLR that was activated, whereas the inflammation exhibited a receptor specific profile in terms of both recruited cells and inflammatory mediators. The inflammatory response caused by LPS appeared to be dependent on MyD88 pathway. Altogether the presented data indicate that the development of AHR and the induction of local inflammation might be the result of two parallel events, rather than one leading to another

Malarial Hemozoin Is a Nalp3 Inflammasome Activating Danger Signal

BACKGROUND: Characteristic symptoms of malaria include recurrent fever attacks and neurodegeneration, signs that are also found in patients with a hyperactive Nalp3 inflammasome. Plasmodium species produce a crystal called hemozoin that is generated by detoxification of heme after hemoglobin degradation in infected red blood cells. Thus, we hypothesized that hemozoin could activate the Nalp3 inflammasome, due to its particulate nature reminiscent of other inflammasome-activating agents. METHODOLOGY/PRINCIPAL FINDINGS: We found that hemozoin acts as a proinflammatory danger signal that activates the Nalp3 inflammasome, causing the release of IL-1beta. Similar to other Nalp3-activating particles, hemozoin activity is blocked by inhibiting phagocytosis, K(+) efflux and NADPH oxidase. In vivo, intraperitoneal injection of hemozoin results in acute peritonitis, which is impaired in Nalp3-, caspase-1- and IL-1R-deficient mice. Likewise, the pathogenesis of cerebral malaria is dampened in Nalp3-deficient mice infected with Plasmodium berghei sporozoites, while parasitemia remains unchanged. SIGNIFICANCE/CONCLUSIONS: The potent pro-inflammatory effect of hemozoin through inflammasome activation may possibly be implicated in plasmodium-associated pathologies such as cerebral malaria

Malarial Hemozoin Is a Nalp3 Inflammasome Activating Danger Signal

BACKGROUND: Characteristic symptoms of malaria include recurrent fever attacks and neurodegeneration, signs that are also found in patients with a hyperactive Nalp3 inflammasome. Plasmodium species produce a crystal called hemozoin that is generated by detoxification of heme after hemoglobin degradation in infected red blood cells. Thus, we hypothesized that hemozoin could activate the Nalp3 inflammasome, due to its particulate nature reminiscent of other inflammasome-activating agents. METHODOLOGY/PRINCIPAL FINDINGS: We found that hemozoin acts as a proinflammatory danger signal that activates the Nalp3 inflammasome, causing the release of IL-1beta. Similar to other Nalp3-activating particles, hemozoin activity is blocked by inhibiting phagocytosis, K(+) efflux and NADPH oxidase. In vivo, intraperitoneal injection of hemozoin results in acute peritonitis, which is impaired in Nalp3-, caspase-1- and IL-1R-deficient mice. Likewise, the pathogenesis of cerebral malaria is dampened in Nalp3-deficient mice infected with Plasmodium berghei sporozoites, while parasitemia remains unchanged. SIGNIFICANCE/CONCLUSIONS: The potent pro-inflammatory effect of hemozoin through inflammasome activation may possibly be implicated in plasmodium-associated pathologies such as cerebral malaria

Microbial Patterns Signaling via Toll-Like Receptors 2 and 5 Contribute to Epithelial Repair, Growth and Survival

Epithelial cells (ECs) continuously interact with microorganisms and detect their presence via different pattern-recognition receptors (PRRs) including Toll-like receptors (TLRs). Ligation of epithelial TLRs by pathogens is usually associated with the induction of pro-inflammatory mediators and antimicrobial factors. In this study, using human airway ECs as a model, we found that detection of microbial patterns via epithelial TLRs directly regulates tissue homeostasis. Staphylococcus aureus (S. aureus) and microbial patterns signaling via TLR2 and TLR5 induce a set of non-immune epithelial responses including cell migration, wound repair, proliferation, and survival of primary and cancerous ECs. Using small interfering RNA (siRNA) gene targeting, receptor-tyrosine kinase microarray and inhibition studies, we determined that TLR and the epidermal growth factor receptor (EGFR) mediate the stimulating effect of microbial patterns on epithelial repair. Microbial patterns signaling via Toll-like receptors 2 and 5 contribute to epithelial repair, growth and survival. This effect is independent of hematopoietic and other cells as well as inflammatory cytokines suggesting that epithelia are able to regulate their integrity in an autonomous non-inflammatory manner by sensing microbes directly via TLRs

CD8+ T Cells and IFN-γ Mediate the Time-Dependent Accumulation of Infected Red Blood Cells in Deep Organs during Experimental Cerebral Malaria

Background: Infection with Plasmodium berghei ANKA (PbA) in susceptible mice induces a syndrome called experimental cerebral malaria (ECM) with severe pathologies occurring in various mouse organs. Immune mediators such as T cells or cytokines have been implicated in the pathogenesis of ECM. Red blood cells infected with PbA parasites have been shown to accumulate in the brain and other tissues during infection. This accumulation is thought to be involved in PbA–induced pathologies, which mechanisms are poorly understood. Methods and Findings: Using transgenic PbA parasites expressing the luciferase protein, we have assessed by real-time in vivo imaging the dynamic and temporal contribution of different immune factors in infected red blood cell (IRBC) accumulation and distribution in different organs during PbA infection. Using deficient mice or depleting antibodies, we observed that CD8 + T cells and IFN-c drive the rapid increase in total parasite biomass and accumulation of IRBC in the brain and in different organs 6–12 days post-infection, at a time when mice develop ECM. Other cells types like CD4 + T cells, monocytes or neutrophils or cytokines such as IL-12 and TNF-a did not influence the early increase of total parasite biomass and IRBC accumulation in different organs. Conclusions: CD8 + T cells and IFN-c are the major immune mediators controlling the time-dependent accumulation of P. berghei-infected red blood cells in tissues

Pathogenic Roles of CD14, Galectin-3, and OX40 during Experimental Cerebral Malaria in Mice

An in-depth knowledge of the host molecules and biological pathways that contribute towards the pathogenesis of cerebral malaria would help guide the development of novel prognostics and therapeutics. Genome-wide transcriptional profiling of the brain tissue during experimental cerebral malaria (ECM ) caused by Plasmodium berghei ANKA parasites in mice, a well established surrogate of human cerebral malaria, has been useful in predicting the functional classes of genes involved and pathways altered during the course of disease. To further understand the contribution of individual genes to the pathogenesis of ECM, we examined the biological relevance of three molecules – CD14, galectin-3, and OX40 that were previously shown to be overexpressed during ECM. We find that CD14 plays a predominant role in the induction of ECM and regulation of parasite density; deletion of the CD14 gene not only prevented the onset of disease in a majority of susceptible mice (only 21% of CD14-deficient compared to 80% of wildtype mice developed ECM, p<0.0004) but also had an ameliorating effect on parasitemia (a 2 fold reduction during the cerebral phase). Furthermore, deletion of the galectin-3 gene in susceptible C57BL/6 mice resulted in partial protection from ECM (47% of galectin-3-deficient versus 93% of wildtype mice developed ECM, p<0.0073). Subsequent adherence assays suggest that galectin-3 induced pathogenesis of ECM is not mediated by the recognition and binding of galectin-3 to P. berghei ANKA parasites. A previous study of ECM has demonstrated that brain infiltrating T cells are strongly activated and are CD44+CD62L− differentiated memory T cells [1]. We find that OX40, a marker of both T cell activation and memory, is selectively upregulated in the brain during ECM and its distribution among CD4+ and CD8+ T cells accumulated in the brain vasculature is approximately equal