Destructive arthritis in a patient with chikungunya virus infection with persistent specific IgM antibodies

<p>Abstract</p> <p>Background</p> <p>Chikungunya fever is an emerging arboviral disease characterized by an algo-eruptive syndrome, inflammatory polyarthralgias, or tenosynovitis that can last for months to years. Up to now, the pathophysiology of the chronic stage is poorly understood.</p> <p>Case presentation</p> <p>We report the first case of CHIKV infection with chronic associated rheumatism in a patient who developed progressive erosive arthritis with expression of inflammatory mediators and persistence of specific IgM antibodies over 24 months following infection.</p> <p>Conclusions</p> <p>Understanding the specific features of chikungunya virus as well as how the virus interacts with its host are essential for the prevention, treatment or cure of chikungunya disease.</p

Molecular Blocking of CD23 Supports Its Role in the Pathogenesis of Arthritis

BACKGROUND: CD23 is a differentiation/activation antigen expressed by a variety of hematopoietic and epithelial cells. It can also be detected in soluble forms in biological fluids. Initially known as the low-affinity receptor for immunoglobulin E (Fc epsilonRII), CD23 displays various other physiologic ligands such as CD21, CD11b/c, CD47-vitronectin, and mannose-containing proteins. CD23 mediates numerous immune responses by enhancing IgE-specific antigen presentation, regulating IgE synthesis, influencing cell differentiation and growth of both B- and T-cells. CD23-crosslinking promotes the secretion of pro-inflammatory mediators from human monocytes/macrophages, eosinophils and epithelial cells. Increased CD23 expression is found in patients during allergic reactions and rheumatoid arthritis while its physiopathologic role in these diseases remains to be clarified. METHODOLOGY/PRINCIPAL FINDINGS: We previously generated heptapeptidic countrestructures of human CD23. Based on in vitro studies on healthy and arthritic patients' cells, we showed that CD23-specific peptide addition to human macrophages greatly diminished the transcription of genes encoding inflammatory cytokines. This was also confirmed by significant reduction of mediator levels in cell supernatants. We also show that CD23 peptide decreased IgE-mediated activation of both human and rat CD23(+) macrophages. In vivo studies in rat model of arthritis showed that CD23-blocking peptide ameliorates clinical scores and prevent bone destruction in a dose dependent manner. Ex-vivo analysis of rat macrophages further confirmed the inhibitory effect of peptides on their activation. Taken together our results support the role of CD23 activation and subsequent inflammatory response in arthritis. CONCLUSION: CD23-blocking peptide (p30A) prevents the activation of monocytes/macrophages without cell toxicity. Thus, targeting CD23 by antagonistic peptide decreases inflammatory markers and may have clinical value in the treatment of human arthritis and allergic reactions involving CD23

Membrane damages in bacteria interacting with silica nanoparticles revealed by AFM

Nanoparticles (NPs) can interact with biological systems, with either negative or positive consequences (potential risks or elimination of pathogenic bacteria). In this context, we investigate the morphology and physico-chemical properties of Escherichia coli bacteria interacting with silica NPs by Atomic Force Microscopy (AFM), this method providing access to topographic information and local rheological properties at the nm scale (with a discrimination between “hard”, NPs, and “soft”, bacteria, materials), either in air or physiological environment. AFM images show that silica NPs tend to aggregate around bacteria, their further action depending on their diameter. The presence of big NPs (100 and 200 nm) does not change E. coli morphology, bacteria remaining rod-shaped and high. The bacterial external membrane keeps also its organization in domains, suggesting that such NPs are too voluminous to penetrate into bacteria. On the contrary, in the presence of small NPs (4 and 10 nm) bacteria adopt unusual spherical shapes, some of them even suffering from a partial collapse, leading to the release of cellular compounds. The external membrane is also disturbed, exhibiting spherical aggregates, which could be due to a reorganization of lipopolysaccharides present in this membrane

Human macrophage tumor necrosis factor TNF-alpha production induced by Trypanosoma brucei gambiense and the role of TNF-alpha in parasite control

#Trypanosoma brucei gambiense$, a causative agent of sleeping sickness, induced a dose-dependent production of tumor necrosis factor (TNF)-alpha by human macrophages in vitro. TNF-alpha was also induced in the Mono Mac 6 cell line, which indicates a direct effect of parasite components on macrophages. Parasite-soluble factors were also potent inducers of TNF-alpha. The addition of anti-TNF-alpha to cocultures of macrophages and parasites increased the number of trypanosomes and their life span, whereas irrevelant antibodies had no effect. TNF-alpha may have a direct role (i.e., direct trypanolytic activity) and/or an indirect one, such as TNF-alpha mediated induction of cytotoxic molecules. A direct dose-dependent lytic effect of TNF-alpha on purified parasites was observed. This lytic effect was inhibited by anti-TNF-alpha. These data suggest that, as in experimental trypanosomiasis, TNF-alpha is involved in parasite growth control in human African trypanosomiasis. (Résumé d'auteur

Membrane damages in bacteria interacting with silica nanoparticles revealed by AFM

International audienceNanoparticles (NPs) can interact with biological systems, with either negative or positive consequences (potential risks or elimination of pathogenic bacteria). In this context, we investigate the morphology and physico-chemical properties of Escherichia coli bacteria interacting with silica NPs by Atomic Force Microscopy (AFM), this method providing access to topographic information and local rheological properties at the nm scale (with a discrimination between “hard”, NPs, and “soft”, bacteria, materials), either in air or physiological environment. AFM images show that silica NPs tend to aggregate around bacteria, their further action depending on their diameter. The presence of big NPs (100 and 200 nm) does not change E. coli morphology, bacteria remaining rod-shaped and high. The bacterial external membrane keeps also its organization in domains, suggesting that such NPs are too voluminous to penetrate into bacteria. On the contrary, in the presence of small NPs (4 and 10 nm) bacteria adopt unusual spherical shapes, some of them even suffering from a partial collapse, leading to the release of cellular compounds. The external membrane is also disturbed, exhibiting spherical aggregates, which could be due to a reorganization of lipopolysaccharides present in this membrane