Neoproterozoic metamorphic events in the kekem area (central domain of the Cameroon north equatorial fold belt): P-T data

The Kekem area (southwestern part of the central domain of the Cameroon North Equatorial Fold Belt) is composed of high-grade migmatitic gneisses in which two lithological units are distinguished: (i) a metasedimentary unit (garnet- sillimanite-biotite-gneisses and garnet-biotite-gneisses) interpreted as a continental series; and (ii) meta-igneous rocks comprising mafic pyroxene gneisses, amphibolites, and orthogneisses. These units recrystallised under HT-MP conditions (T=700-800‹C, P . 0.5-0.8GPa) and were deformed in relation to a major tangential tectonic event with the NNE-SSW kinematic direction. The lithological association and its tectono-metamorphic evolution show striking similarities with the Banyo and Maham III gneisses, suggesting that the extensional depositional environment envisaged for this formation can be extended farther west. P-T calculations in this contribution provide new data on the Pan-African structural and metamorphic evolution of the metapelites and metabasites in the basement of the Kekem area. The results show two distinct events: (1) crystallization during a Pan-African high temperature metamorphic event and, (2) subsequent deformation and high temperature mylonitization. The data imply a high-temperature amphibolite-facies metamorphism along a clockwise P-T path. The recorded P-T involves a marked variation in pressure, which is typical of collisional crustal thickening. The contrasted metamorphic evolution between areas located to the south of the Central Cameroon Shear Zone(CCSZ; high pressure: Yaounde, Ntui-Betamba), and those located to the north (low pressure: Banyo, Tibati), along with widespread remains of Paleoproterozoic crust, suggest important crustal thickening during Pan-African tangential tectonics in southern Cameroon. As a consequence, the CCSZ is not simply a late Pan-African transpressive shear zone but appears to have been formerly a major intracontinental thrust zone.Key words: HT metamorphic event / Kekem/ Cameroon / Collisional crustal thickening / Neoproterozoic /North Equatorial Fold Belt.La region de Kekem est formee de gneiss anatectiques de haut-degre dans lesquels deux ensembles sont reconnus: (i) un ensemble metasedimentaire (gneiss a grenat, sillimanite et biotite, et gneiss a grenat et biotite) considere comme depose a lLinterieur dLun continent, (ii) des roches meta-ignees comprenant des gneiss a grenat et pyroxene,des amphibolites de composition mafique, et des orthogneiss. Ces deux ensembles ont recristallise (T=700-800‹C, P. 0,5-0,8GPa) et ont ete deformes en relation avec un episode majeur de tectonique tangentielle de direction cinematique NNE-SSW. Cette association lithologique et son evolution tectono-metamorphique montrent une similitude remarquable avec les formations panafricaines de Banyo et Maham III du domaine central de la chaine, suggerant que le contexte extensif de depot envisage pour ces dernieres peut etre etendu plus a lLouest. Les donnees nouvelles sur lLevolution tectono-metamorphique des metasediments et des metabasites panafricains du socle de la region de Kekem mettent en evidence un metamorphisme panafricain de haute temperature suivi dLune mylonitisation a haute temperature dans le facies amphibolite de haut degre selon un chemin P-T horaire. Les conditions P-T enregistrees se caracterisent par une variation de pression typique dLun epaississement crustal. LLevolution metamorphique panafricaine contrastee entre le domaine au sud du cisaillement Centre Camerounais(CCC; haute pression: Yaounde, Ntui-Betamba) et le domaine nord-CCC (basse a moyenne pression: Banyo, Tibati) ainsi que la presence ubiquiste de reliques dLune croute ancienne paleoproterozoique, suggerent un important epaississement crustal, lors dLun episode de tectonique tangentielle. Le CCC nLest donc pas un simple accident panafricain transpressif, mais apparait bien avoir ete prealablement un  chevauchement intracontinental majeur.Mots-cles : Metamorphisme de Haut degre/Kekem/ Cameroun/ Epaississement crustal/ Neoproterozoique /Chaine Nord Equatoria

Механические и триботехнические свойства композитов на основе полифениленсульфида, армированных различными микроволокнами

In macrophages, two signaling pathways, dependent on MyD88 or TIR domain-containing adaptor-inducing IFN-β (TRIF) signaling, emanate from the LPS receptor TLR4/MD-2. In this study, we show that in murine bone marrow-derived mast cells (BMMCs), only the MyD88-dependent pathway is activated by LPS. The TRIF signaling branch leading both to NF-κB activation and enhanced proinflammatory cytokine production, as well as to IRF3 activation and subsequent IFN-β production, is absent in LPS-stimulated BMMCs. IRF3 activation is also absent in peritoneal mast cells from LPS-injected mice. We observed strongly diminished TRAM expression in BMMCs, but overexpression of TRAM only moderately enhanced IL-6 and did not boost IFN-β responses to LPS in these cells. A combination of very low levels of TRAM and TLR4/MD-2 with the known absence of membrane-bound CD14 are expected to contribute to the defective TRIF signaling in mast cells. We also show that, unlike in macrophages, in BMMCs the TRIF-dependent and -independent IFN-αβ responses to other recognized IFN inducers (dsRNA, adenovirus, and B-DNA) are absent. These results show how the response to the same microbial ligand using the same receptor can be regulated in different cell types of the innate immune system

Inflammation-Induced Acid Tolerance Genes gadAB in Luminal Commensal Escherichia coli Attenuate Experimental Colitis

ABSTRACT Dysregulated immune responses to commensal intestinal bacteria, including Escherichia coli , contribute to the development of inflammatory bowel diseases (IBDs) and experimental colitis. Reciprocally, E. coli responds to chronic intestinal inflammation by upregulating expression of stress response genes, including gadA and gadB . GadAB encode glutamate decarboxylase and protect E. coli from the toxic effects of low pH and fermentation acids, factors present in the intestinal lumen in patients with active IBDs. We hypothesized that E. coli upregulates gadAB during inflammation to enhance its survival and virulence. Using real-time PCR, we determined gadAB expression in luminal E. coli from ex-germfree wild-type (WT) and interleukin-10 (IL-10) knockout (KO) (IL-10 −/− ) mice selectively colonized with a commensal E. coli isolate (NC101) that causes colitis in KO mice in isolation or in combination with 7 other commensal intestinal bacterial strains. E. coli survival and host inflammatory responses were measured in WT and KO mice colonized with NC101 or a mutant lacking the gadAB genes (NC101Δ gadAB ). The susceptibility of NC101 and NC101Δ gadAB to killing by host antimicrobial peptides and their translocation across intestinal epithelial cells were evaluated using bacterial killing assays and transwell experiments, respectively. We show that expression of gadAB in luminal E. coli increases proportionately with intestinal inflammation in KO mice and enhances the susceptibility of NC101 to killing by the host antimicrobial peptide cryptdin-4 but decreases bacterial transmigration across intestinal epithelial cells, colonic inflammation, and mucosal immune responses. Chronic intestinal inflammation upregulates acid tolerance pathways in commensal E. coli isolates, which, contrary to our original hypothesis, limits their survival and colitogenic potential. Further investigation of microbial adaptation to immune-mediated inflammation may provide novel insights into the pathogenesis and treatment of IBDs

High susceptibility to lipopolysaccharide-induced lethal shock in encephalomyocarditis virus-infected mice

Secondary bacterial infection in humans is one of the pathological conditions requiring clinical attention. In this study, we examined the effect of lipopolysaccharide (LPS) on encephalomyocarditis virus (EMCV) infected mice. All mice inoculated with EMCV at 5 days before LPS challenge died within 24 h. LPS-induced TNF-α mRNA expression was significantly increased in the brain and heart at 5 days after EMCV infection. CD11b+/TLR4+ cell population in the heart was remarkably elevated at 5 days after EMCV infection, and sorted CD11b+ cells at 5 days after EMCV infection produced a large amount of TNF-α on LPS stimulation in vivo and in vitro. In conclusion, we found that the infiltration of CD11b+ cells into infected organs is involved in the subsequent LPS-induced lethal shock in viral encephalomyocarditis. This new experimental model can help define the mechanism by which secondary bacterial infection causes a lethal shock in viral encephalomyocarditis

TLR9-Dependent and Independent Pathways Drive Activation of the Immune System by Propionibacterium Acnes

Propionibacterium acnes is usually a relatively harmless commensal. However, under certain, poorly understood conditions it is implicated in the etiology of specific inflammatory diseases. In mice, P. acnes exhibits strong immunomodulatory activity leading to splenomegaly, intrahepatic granuloma formation, hypersensitivity to TLR ligands and endogenous cytokines, and enhanced resistance to infection. All these activities reach a maximum one week after P. acnes priming and require IFN-γ and TLR9. We report here the existence of a markedly delayed (1–2 weeks), but phenotypically similar TLR9-independent immunomodulatory response to P. acnes. This alternative immunomodulation is also IFN-γ dependent and requires functional MyD88. From our experiments, a role for MyD88 in the IFN-γ-mediated P. acnes effects seems unlikely and the participation of the known MyD88-dependent receptors, including TLR5, Unc93B-dependent TLRs, IL-1R and IL-18R in the development of the alternative response has been excluded. However, the crucial role of MyD88 can partly be attributed to TLR2 and TLR4 involvement. Either of these two TLRs, activated by bacteria and/or endogenously generated ligands, can fulfill the required function. Our findings hint at an innate immune sensitizing mechanism, which is potentially operative in both infectious and sterile inflammatory disorders

Innate, antigen-independent role for T cells in the activation of the immune system by Propionibacterium acnes

Propionibacterium acnes is a human commensal but also an opportunistic pathogen. In mice, P. acnes exerts strong immunomodulatory activities, including formation of intrahepatic granulomas and induction of LPS hypersensitivity. These activities are dependent on P. acnes recognition via TLR9 and subsequent IL-12-mediated IFN-γ production. We show that P. acnes elicits IL-12p40 and p35 mRNA expression in macrophages, and IFN-γ mRNA in liver CD4+ T cells and NK cells. After priming with P. acnes, CD4+ T cells serve as the major IFN-γ mRNA source. In the absence of CD4+ T cells, CD8+ T cells (regardless of antigenic specificity) or NK cells can produce sufficient IFN-γ to induce the P. acnes-driven immune effects. Moreover, in the absence of αβT cells, γδT cells also enable the development of strongly enhanced TNF-α and IFN-γ responses to LPS and intrahepatic granuloma formation. Thus, under microbial pressure, different T-cell types, independent of their antigen specificity, exert NK-cell-like functions, which contribute decisively to the activation of the innate immune system

Lipopolysaccharide sensing an important factor in the innate immune response to Gram-negative bacterial infections: Benefits and hazards of LPS hypersensitivity

In this review, we summarize our investigations concerning the differential importance of CD14 and LBP in toll-like receptor 4 (TLR4)/myeloid differentiation protein-2 (MD-2)-mediated signaling by smooth and rough-form lipopolysaccharide (LPS) chemotypes and include the results obtained in studies with murine and human TLR4-transgenic mice. Furthermore, we present more recent data on the mechanisms involved in the induction of LPS hypersensitivity by bacterial and viral infections and on the reactivity of the hypersensitive host to non-LPS microbial ligands and endogenous mediators. Finally, the effects of pre-existing hypersensitivity on the course and outcome of a super-infection with Salmonella typhimurium or Listeria monocytogenes are summarized

Absence of TRIF Signaling in Lipopolysaccharide-Stimulated Murine Mast Cells

In macrophages, two signaling pathways, dependent on MyD88 or TIR domain-containing adaptor-inducing IFN-β (TRIF) signaling, emanate from the LPS receptor TLR4/MD-2. In this study, we show that in murine bone marrow-derived mast cells (BMMCs), only the MyD88-dependent pathway is activated by LPS. The TRIF signaling branch leading both to NF-κB activation and enhanced proinflammatory cytokine production, as well as to IRF3 activation and subsequent IFN-β production, is absent in LPS-stimulated BMMCs. IRF3 activation is also absent in peritoneal mast cells from LPS-injected mice. We observed strongly diminished TRAM expression in BMMCs, but overexpression of TRAM only moderately enhanced IL-6 and did not boost IFN-β responses to LPS in these cells. A combination of very low levels of TRAM and TLR4/MD-2 with the known absence of membrane-bound CD14 are expected to contribute to the defective TRIF signaling in mast cells. We also show that, unlike in macrophages, in BMMCs the TRIF-dependent and -independent IFN-αβ responses to other recognized IFN inducers (dsRNA, adenovirus, and B-DNA) are absent. These results show how the response to the same microbial ligand using the same receptor can be regulated in different cell types of the innate immune system

Requirement for TLR9 in the Immunomodulatory Activity of Propionibacterium acnes¹

Propionibacterium acnes (formerly Corynebacterium parvum) is part of the human flora and, as such, is associated with several human pathologies. It possesses strong immunomodulatory activities, which makes this bacterium interesting for prophylactic and therapeutic vaccination. The bacterial component(s) and the host receptor(s) involved in the induction of these activities are poorly understood. We show in this study that TLR9 is crucial in generating the characteristic effects of killed P. acnes priming in the spleen, such as extramedullary hemopoiesis and organ enlargement, and granuloma formation in the liver. Furthermore, the ability to overproduce TNF-α and IFN-γ in response to LPS, lipid A, synthetic lipopeptide Pam3CysK4, or whole killed bacteria was present in P. acnes-primed wild-type, but not TLR9-/-, mice. Finally, P. acnes priming failed to induce enhanced resistance to murine typhoid fever in TLR9-/- mice. Thus, TLR9 plays an essential role in the induction of immunomodulatory effects by P. acnes. Because IFN-γ is a key mediator of these effects, and enhanced IFN-γ mRNA expression was absent in spleen and liver of P. acnes-primed TLR9-/- mice, we conclude that TLR9 is required for the induction of IFN-γ by P. acnes