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Biomedical subjects

Monique Capron

Publications and source records attributed to Monique Capron.

52 records · Page 3Linked to original sources

Pulmonary coinfection by Trichomonas vaginalis and Pneumocystis sp. as a novel manifestation of AIDS.

A 41-year-old man was hospitalized, presenting increasing dyspnea and extensive ground-glass opacities on chest X-ray. Infection by human immunodeficiency virus was confirmed. Cytologic examination of bronchoalveolar lavage fluid revealed numerous trichomonads and aggregates of Pneumocystis sp. Treatment was followed by rapid improvement of respiratory symptoms and chest X-ray. The trichomonad species found in the lungs was identified as Trichomonas vaginalis by small-subunit rRNA gene amplification and sequencing. With the exception of rare cases of contamination of newborn babies during delivery, T. vaginalis has never been found in lungs in healthy or immunocompromised adults. In the present case, T. vaginalis is found as coinfecting agent. Our data, like those found in the literature, suggest that trichomonads are overlooked parasites that may be regularly implicated in diverse human pathologies.

AIDS-Related Opportunistic Infections↗

An unusual receptor tyrosine kinase of Schistosoma mansoni contains a Venus Flytrap module.

Previous studies have suggested that successful development of the parasitic helminth Schistosoma mansoni must be dependent on an adaptative molecular dialogue with its hosts and on the existence of receptors for growth factors and hormones. Attempts to identify a homolog of the insulin receptor (IR) have led us to characterize a new receptor tyrosine kinase (RTK) molecule in S. mansoni. SmRTK-1 is an integral membrane protein with a single membrane-spanning sequence separating an extracellular ligand-binding domain and a cytoplasmic TK domain. Structural and phylogenetic analyses of the kinase domain of SmRTK-1 confirmed its similarity to IR catalytic domains. However, sequence analysis of the extracellular domain of SmRTK-1 revealed similarity with various proteins (such as drug receptors) that share a structure known as the Venus Flytrap (VFT) module. Alignment with other VFT modules for which the structure has been solved was used to generate a 3D model of the putative VFT module of SmRTK-1. Phylogenetic analysis indicated that the SmRTK-1 VFT module was closer to that of the GABA(B) receptor. Numerous RTK genes recently discovered in vertebrate and invertebrate species code for large families of modular proteins with diverse structures and ligand-binding specificities. SmRTK-1 probably represents a new class of RTK whose function remains to be determined. RTKs are present in all metazoans and associated with the control of metabolism, growth and development. The preferential localization of SmRTK-1 in sporocyst germinal cells and ovocytes could be in favor of its function in schistosome growth and differentiation.

Amino Acid Sequence↗

Differential production in vitro of antigen specific IgG1, IgG3 and IgA: a study in Schistosoma haematobium infected individuals.

This study has evaluated the individual control of isotype production and the influence of external signals that can be experimentally provided in vitro, in antibody responses to two different recombinant Schistosoma antigens (Sh28GST and TPx-1). Peripheral blood mononuclear cells or enriched B cell fractions obtained from S. haematobium infected Senegalese adults were induced to terminal differentiation in vitro. The production of antibody to either antigen was donor-dependent and for each donor it was antigen-dependent. Differentiation to IgG1 and IgG3 production, and possibly IgA, specific to these conserved parasite antigens could be regulated differentially in vitro. Exogenous IL-2 and IL-10 or IL-10 and TGF-beta led to the production of specific IgG3 or IgG1 and/or IgA, respectively. This is the first report on such experimentally induced differential regulation of antigen-specific IgG1 and IgG3. This may have implications in designing protocols for protein based-vaccinations aiming at eliciting antibody responses of certain protective-type isotypes.

Adolescent↗

Cell death in protists without mitochondria.

Some protozoans, such as Trichomonad species, do not possess mitochondria. Most of the time, they harbor another type of membrane-bounded organelle, called hydrogenosome from its capacity to produce H(2). This is the case for the human parasite Trichomonas vaginalis. Some other parasites, such as the protist Giardia lamblia, do not harbor any of these organelles. From this observation arises naturally a naive question: How do cells die when the mitochondrion, the cornerstone of apoptotic process, is absent? Data strongly suggest that the mitochondrion and the hydrogenosome arose from a common ancestral endosymbiont. But hydrogenosomes do not appear to directly substitute for mitochondria in apoptotic functions. Thus, it appears judicious to examine more closely the genome of unicellular cells, which do not harbor mitochondria, and search for new molecules that could participate in the apoptotic process in these microorganisms.

Animals↗

Chloroquine and artemisinin: six decades of research--what next?

Over the next decade drugs will remain the focus of continuous efforts to control malaria, with a contribution from pharmacogenomic development. Quinine, extracted from Cinchona bark, has been the source for aminoquinoline drugs such as chloroquine; more recently, artemisinin extracted from Artemisia allowed the design of artemisinin mimics containing a trioxane structure. Here, we examine parallels between chloroquine and artemisinin in terms of pharmacological target discovery, mechanism of action and parasite resistance. The widespread use of chloroquine has dramatically reduced its therapeutic response, thus recent strategies are based on artemisinin combinations.

Animals↗

Antigen presentation by CD1d contributes to the amplification of Th2 responses to Schistosoma mansoni glycoconjugates in mice.

During murine schistosomiasis, there is a gradual switch from a predominant Th1 cytokine response to a Th2-dominated response after egg laying, an event that favors the formation of granuloma around viable eggs. Egg-derived glycoconjugates, including glycolipids, may play a crucial role in this phenomenon. In this study, we used a model of dendritic cell sensitization to study the role of egg glycoconjugates in the induction of specific immune response to soluble egg Ag (SEA) and to investigate the possibility that CD1d, a molecule implicated in glycolipid presentation, may be involved in such a phenomenon. We show that, when captured, processed, and presented to naive T lymphocytes by dendritic cells, egg, but not larval, Ag skew the immune response toward a Th2 response. Periodate treatment reversed this effect, indicating that the sugar moiety of SEA is important in this phenomenon. Using DC treated ex vivo with a neutralizing anti-CD1d Ab or isolated from CD1d knockout mice, we show that CD1d is crucial in the priming of SEA-specific Th2 lymphocytes. We then evaluated the contribution of CD1d on the development of the SEA-specific immune response and on the formation of the egg-induced liver granuloma during murine schistosomiasis. We find that CD1d knockout mice have a reduced Th2 response after egg laying and develop a less marked fibrotic pathology compared with wild-type mice. Altogether, our results suggest that Ag presentation of parasite glycoconjugates to CD1d-restricted T cells may be important in the early events leading to the induction of Th2 responses and to egg-induced pathology during murine schistosomiasis.

Animals↗

Molecular phylogeny of parabasalids inferred from small subunit rRNA sequences, with emphasis on the Devescovinidae and Calonymphidae (Trichomonadea).

Small subunit rRNA sequences were obtained by polymerase chain reaction from trichomonad symbionts of termites that belong to the polymastigont Calonymphidae, including Snyderella tabogae, Calonympha grassii, and Metacoronympha senta. The yet-unidentified sequence Nk9 previously obtained from the termite Neotermes koshunensis, has also been shown to derive from the Devescovinidae Devescovina sp. by in situ hybridization. These new sequences were analyzed by distance, parsimony, and likelihood methods in a broad phylogeny including all identified parabasalid sequences available in databases. All analyses revealed the emergence of a very well supported Devescovinidae/Calonymphidae group but showed an unexpected dichotomy of the Calonymphidae represented by the "Coronympha" and "Calonympha" groups. It strongly suggests that the polymastigont state observed in the Calonymphidae might be explained by at least two independent evolutionary events. In a second phylogenetic analysis, some yet-unidentified parabasalid sequences likely deriving from the Devescovinidae/Calonymphidae taxa, were added to our data set. This analysis confirmed the polyphyly of the Calonymphidae. A tentative identification is proposed for each of these sequences, and hypotheses on the origin of the Devescovinidae and Calonymphidae are discussed. Tritrichomonas foetus or a close relative might be the best candidate for the ancestor of the Devescovinidae, fairly consistent with morphology-based hypotheses. Regarding the Calonymphidae, the origin of the "Coronympha" group might be found within the Devescovinidae, related to Foaina, whereas the "Calonympha" group may directly descend from Tritrichomonas or related species.

Animals↗

Vaccine development against schistosomiasis from concepts to clinical trials.

Schistosomiasis is still a major helminth infection at the beginning of the 21st century and an important public health problem in many non-industrialised countries. As the second major parasitic disease in the world after malaria, schistosomiasis affects 200 million people, 800 million being exposed to the risk of infection. It is also estimated that 20 million individuals suffer from severe consequences of this chronic and debilitating disease responsible for at least 500,000 deaths per year.

Animals↗

CCR3-blocking antibody inhibits allergen-induced eosinophil recruitment in human skin xenografts from allergic patients.

Eosinophil, basophil, and T helper 2 (TH2) cell recruitment into tissues is a characteristic feature of allergic diseases. These cells have in common the expression of the chemokine receptor CCR3, which may represent a specific pathway for their accumulation in vivo. Although animal models of allergic reactions are available, findings cannot always be extrapolated to man. To overcome these limitations, we have developed a humanized mouse model of allergic cutaneous reaction using severe combined immunodeficiency mice engrafted with skin and autologous peripheral blood mononuclear cells from allergic donors. Intradermal injection of the relevant allergen into human skin xenografts from allergic individuals induced a significant recruitment of human CD4(+) T cells, basophils, and TH2-type cytokine mRNA-expressing cells, as well as murine eosinophils. Human skin xenografts, atopic status, and autologous peripheral blood mononuclear cell reconstitution were all mandatory to induce the allergic reaction. Next, we addressed the role of CCR3 in the endogenous mechanisms involved in the inflammatory cell recruitment in this experimental model of allergic cutaneous reaction. In vivo administration of an anti-human CCR3-blocking antibody selectively reduced accumulation of eosinophils but not that of CD4(+) cells, basophils, or cells expressing mRNA for TH2-type cytokines. These findings establish a new in vivo model of humanized allergic reaction and suggest that eosinophil migration is mediated mainly through CCR3. Finally, these results suggest that this model might be useful to test human-specific antiallergic modulators.

Allergens↗

[Eosinophils, parasites and allergy: from the biological to the clinical].

Eosinophils have been considered for a long time as secondary cells, only able to be attracted by chemotactic factors and recruited from blood to tissues, at the site of inflammation. More recent studies have shown that their functions are not limited to the release of cytotoxic mediators, effector against parasitic targets but deleterious for tissues in allergy, but they can also participate in the regulation of immune response by producing type 1 and type 2 cytokines. Although questionable, animal models indicate a rather beneficial role of eosinophils in parasitic infections but a detrimental one in allergy. The results of clinical trials aiming at increasing or decreasing respectively their effects are discussed.

Animals↗

Human eosinophils express and release IL-13 following CD28-dependent activation.

Human eosinophils produce a large number of cytokines, including immunoregulatory cytokines. Given that eosinophils store and release interleukin (IL)-4, a key cytokine in the pathogenesis of allergic inflammation, and that IL-4 and IL-13 share common biological functions, we investigated the possibility that IL-13 may be synthesized by these cells. Using flow cytometry and immunocytochemistry, we show that eosinophils synthesize and store IL-13. Granule localization was demonstrated after subcellular fractionation, and IL-13 immunoreactivity was localized to crystalloid, granule-enriched fractions. Furthermore, electron microscopic analyses specifically localized IL-13 to the dense cores of bicompartmental secondary granules. Upon CD28 ligation, IL-13 was released by eosinophils, whereas a combination of CD28 and immunoglobulin A complexes resulted in decreased IL-13 secretion. Furthermore, eosinophil-derived IL-13 exerts a biological effect, inducing CD23 expression on B cells. By having the capacity to synthesize and release IL-13, eosinophils may participate in the development and maintenance of the T helper cell type 2 response, a prominent feature of allergic diseases.

CD28 Antigens↗

Frequency of trichomonads as coinfecting agents in Pneumocystis pneumonia.

OBJECTIVE: To investigate the incidence of the association of Trichomonas and Pneumocystis in the lung. STUDY DESIGN: Sixty-six bronchoalveolar lavage fluid (BALF) samples from immunocompromised patients with pneumocystosis were retrospectively examined microscopically. RESULTS: Trichomonads were found as coinfecting agents in 60% of BALF samples. The frequency and abundance of trichomonads was increased, up to 100%, in cases rich in Pneumocystis. CONCLUSION: The data suggest that pulmonary Trichomonas infection occurs frequently in the course of Pneumocystis pneumonia. The role of trichomonads in causing alveolar damage during Pneumocystis pneumonia is hypothetical.

Animals↗