|Histotechnology and Pathology|
|HEAD||Michel-René HUERRE / email@example.com|
|MEMBERS||Alonso Françoise, secretary, full-time / Avé Patrick, technician, full-time / Cardona Ana, DVM, PhD, full-time / Chimy Marie-Christine, technician, part-time (20%) / Cumont Marie-Christine, full-time / Droin Sabrina, technician, full-time / Fiette Laurence, DVM, PhD, full-time / Huerre Michel, MD, full-time / Jouvion Grégory, DVM, PhD, full-time / Khun Huot, technician, full-time / Legars Mathieu, student (DEA), part-time (20%) / Matondo Jeanne, laboratory assistant, part-time, (80%) / Maurin Sabine, technician, part-time (50%)
Our research programs in 2005-2007 focused on the pathology of infectious diseases, in both humans and experimental animal models, and the study of brain neuroreceptors for quantitative autoradiography using radioimagers (Beta-Imager and Micro-Imager)
1. Pathology and pathogenesis of infectious diseases
Histological patterns and kinetics of the inflammatory process have been studied as a function of the human pathogen and target organ (respiratory and digestive systems, vascular tree, lymph nodes, etc.), in several models.
1.1. Lung pathology (acute and chronic disease)
- Acute diseases: Various pathogens, including viruses and bacteria, can cause acute lung injury. Myxoviruses and coronaviruses infect the epithelial cells of the pharynx and bronchi, resulting in the destruction of these epithelia and the focal recruitment of inflammatory cells. Clostridium sordelli lethal toxin (collaboration with B. Geny, M. Popoff) reproduces the fatal toxic shock syndrome observed in humans and animals, with early massive extravasation of blood in the thoracic cavity. Lung endothelial cell injury increases vascular permeability, but this model is remarkable in that no inflammatory process is observed in other organs. Bacillus anthracis causes acute infection in animal models. Bacilli rapidly cross the pharynx epithelia, and then induce bronchopneumonia. Other models of experimental pneumonia have been studied. Bacterial lipopolysaccharides (LPS), such as NeisseriaLPS (collaboration with J.M. Alonso) and Pseudomonas aeruginosa LPS (collaboration with M. Chignard), rapidly induce exudate production and the local recruitment of polymorphonuclear cells (PMN cells). Aspergillus fumigatus conidia germinate within a few hours of infection, generating hyphae that cross the endothelia and invade the alveolar walls, although PMN cells have been shown to destroy hyphae in experiments using vinblastin (collaboration with M. Chignard and the team of J.P. Latgé) Several mutant strains have been tested and shown to induce lesions in both neutropenic and corticosteroid-treated mice, indicating an important role for host factors in invasive aspergillosis.
- Chronic lung inflammation may be induced by mycobacteria, which can persist in the alveoli and induce granulomatous lesions (collaboration with C. Leclerc, L. Majlessi, and B. Gicquel). Several experiments have been carried out to investigate the relationship between the pattern of lesions and the pathogenicity of the strain (Mt, BCG, BCG RD1 and non tuberculous mycobacteria) or host immune status in transgenic mice. In collaboration with the Immunoregulation Laboratory (G. Marchal), we have investigated the role of BCG bovisin preventing the airway hyperresponsiveness typical of asthma.
1.2. Digestive pathology
1.2.1 Helicobacter pylori(Hp). HPinduces chronic gastritis in humans. We are currently carrying out a multicentre study in collaboration with the International Network of Pasteur Institutes (Dakar, Antananarivo, Pnom Penh, Algiers, Athens). These studies aim to assess the genetic diversity of Hp,using more than 1,000 isolates from multiple sites around the world, and comparing these strains with strains from populations with a high incidence of Hpinfection and stomach cancer.
We have also investigated experimental models, focusing particularly on the role of the αand βcarbonic anhydrases of Hpand NF-kB activation in mice, in collaboration with the team of A. Labigne.
1.2.2. An experimental model of leptospirosis has been studied in collaboration with the team of M. Picardeau. Typical leptospirosis lesions were observed in the liver and the kidney with wild-type Leptospira interrogans,whereas disruption of the ompA-like gene abolished the pathogenicity and virulence of this species, resulting in an absence of typical lesions in the targeted organs.
1.3 Vascular pathology: the endothelium as a target of infection
Kaposi diseases and human herpes virus 8 (HHV8). In collaboration with the team of A. Gessain, we carried out a multicentre study of Kaposi diseases in patients of different geographical origins, which suggested a multiclonal origin for multicentric advanced Kaposi sarcoma lesions.
- Infection studies of the midgut and salivary glands of Aedes albopictuswith the dengue and Chikungunya arboviruses (collaboration with the team of A. Failloux).
- Study of an experimental model of plague (collaboration with the team of E. Carniel).
Quantitative autoradiography based on the use of radioimagers (Beta-Imager and Micro-Imager)
Radioimagers provide an alternative to film autoradiography for in situquantitative studies of tissue sections. They can detect tritium and the usual beta-emitting isotopes in electrophoresis gels or membranes, tissue sections on glass slides and whole-body sections. Their major applications are: receptology (localisation and characterisation of isatin 5-hydroxyoxindole and acetyl choline receptors on brain sections),in situhybridisation pattern of SLC25A12 expression during human prenatal development), in vivopharmacokinetics and the biodistribution of molecules (xindole and indole compounds, increases in the urinary excretion of which have been linked to human neurodegenerative diseases).
Viala J., Chaput C., Boneca I.G., Cardona A., Giradin S.E., Moran A.P., Huerre M.R., Coyle A.J., di Stephano P., Sansonetti P., Labigne A., Bertin J., Philpott D., Ferrero R. Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cagpathogenicity island. Nature Immunology, 2004, 5(11): 1166-1174
Blanchet F., Cardona A., Letimier F.A., Hershfield M.S., Acuto O. CD28 co-stimulatory signal induces protein arginine methylation in T cells. Journal of Experimental Mededecine, 2005, 202(3): 371-377
Al Halabiah, A, Delezoideb A.L., Cardona A., Moalica J.M., Simonneau M. Expression pattern of NOGO and NgR genes during human development. Gene Expression Patterns, 2005, 5(4): 561-568
Abadie V., Badell E., Douillard P., Ensergueix D., Leenen P.J.M., Tanguy M., Fiette L., Saeland S., Gickel B., Winter N. Neutrophils rapidly migrate via lymphatics after Mycobacterium bovisBCG intradermal vaccination and shuttle live bacilli to the draining lymph node. Blood, 2005, 106(5): 1843-1850
Buffet P.A., Milon G., Brousse V., Correas J.M., Dousset B., Couvelard A., Kianmanesh R., Farges O., Sauvanet O., Paye F., Ungeheuer M.N., Ottone C., Khun H.,Fiette L., Guigon G., Huerre M.R., Mercereau-Puijalon O., David P.H. Ex-vivoperfusion of human spleens maintains clearing and processing functions. Blood, 2006, 107(9): 3745-37
Geny B., Khun H.,Fitting G.C., Zarantonelli L., Mazuet C., Cayet N., Szatanik M., Prevost M.C., Cavaillon J.M., Huerre M.R., Popoff M.R. Clostridium sordelliilethal toxin kills mice by inducing a major increase in lung vascular permeability. American Journal of Patholology, 2007, 170 (3): 1003-17
Glomski I.J., Huerre M.R.,Mock M., Goossens P. Primary involvement of pharynx and Peyer’s patch in inhalational and intestinal anthrax. PLoS pathogen . 2007, 3(6): e76
Duprez R., Lacoste V., Briere J., Couppié P., Camilles F., Sainte Marie D., Kassa-Kehlembo E., Lando M.J., Essame-Oyono J.L., Nkegoun B., Hbid O., Mahé A., Huerre M.R., Gessain A. Evidence for a multiclonal origin of multicentric advanced lesions of Kaposi sarcoma. Journal of the National Cancer Institute, 2007, 99(14): 1086-1094
Activity Reports 2007 - Institut Pasteur
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