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  Hispat


  Director : Michel Huerre (mhuerre@pasteur.fr)


  abstract

 

The unit of Histotechnology and Pathology has studied various bacterial infections (Mycobacteria, Helicobacter, Shigella, Listeria, Bordetella), viral (Dengue, Rift Valley virus), parasitic (Entamoeba, Leishmania) and mycotic infections (Aspergillus). We study also morphological consequences of inactivation of differents transcription factors (vHNF1, HNF1, SNF5) in development and in neoplasia. In collaboration with other units, we have developped, in experimental pathology the quantitative analysis on tissues sections in using a new resolution radioimager techniques for the detection, localization and characterization of radiolabelled molecules.



  report

cale

1) Digestive infectious diseases.

a) Mutagenic effect associated with Helicobacter infection.

We are involved in a transversal research program, beside A. Labigne and R. Ferrero (Unité de Pathogénie Bactérienne des Muqueuses), M. Hofnung and E. Touati (Unité de Programmation Moléculaire et Toxicologie Génétique) the mutagenic effect of the infection by Helicobacter and the influence of salted consumption using the transgenic mouse Big Blue l Lac I. The progression from chronic gastritis to metaplasia, dysplasia then to gastric neoplasia during Helicobacter pylori chronic infection is demonstrated in human pathology. As previously observed, mice chronically infected with H. pylori or H. felis develop a chronic gastritis 6 and 12 months p.i., no neoplasm in Big Blue mice has been observed but frequency of mutations in the transgene used as an indicator is increased.

b) Interaction between Listeria/ and digestive epithelium.

P. ossart et M. Lecuit (Unité Interactions Bactéries-Cellule) have shown that E-cadhérine, expressed by epithelial cells is the specific ligand of the bacterial internalin that permits pathogenic Listeria to cross the. Using immunohistochemoistry, We have observed that only Listeria expressing internaline are entero-invasives, in guinea pig or in mice transgenic for the human E-cadherin.

b) Interaction between Shigella and digestive epithelium.

We work with Ph. Sansonetti, and A. Phalippon (Unité de Pathogénie Microbienne des Muqueuses) who study the interaction between Shigella and intestinal epithelium, the role of the inflammatory response. We have continued the morphological analysis of Shigella infection in immunodeficient mice devoid of T lymphocytes or IFNg . We have also validated a murine model of lung infection, since mouse is not susceptible to digestive infection by Shigella.

2) Hepatic diseases

a) Viral infections of the liver

In collaboration with Pasteur Insitute of Vietnam, pediatric hospital Ho Chi Minh Ville, we have demonstrated in human biopsies that the liver is the major target of Dengue virus. Histological lesions show a midzonal necrosis, steatosis and presence of Councilman bodies containing viral antigens. Hepatocytes and Kupffer cells are the targets cells where the replication occurs. Fulminant hepatitis induced with Rift Valley virus shows similar lesions in a mouse model.(coll. M. Bouloy, Unité des Arbovirus).

b) Amebiasis

We are involved in a collaboration with M.C. Rigothier (Faculté de Pharmacie de Chatenay-Malabry) and N. Guillen (Unité de Biologie Cellulaire du Parasitisme), in which we compare in hamster lesions associated with infection by mutants strains of Entamoeba histolytica to those induced by the wild one.

3-Dendritic cells

We have carried on different projects focusing in the interaction between dendritic cells and pathogens intradermal infection by Leishmania, (L. Elies with Th. Lang, J.-C. Antoine, Unité d'Immunophysiologie et Parasitisme intracellulaire) or B.C.G (L. Elies, with N. Winter, Unité de Génétique Mycobactérienne), interaction of de Bordetella with the N.A.L.T. (N. Guiso, P. Gueirard, Unité des Bordetelles).

We also studied the role of splenic dendritic cells and their APC function after administration of live mycobacteria (BCG) and mutant strains of Mycobacteria with E. Pivert.

4- Role of the transcription factors HNF1, vHNF1, SNF5.

We are involved in the study of role of differentv transcription factors in liver development using knock-out mice for vHNF1, vHNF1/HNF, SNF5 (coll. L. Gresh, C. Cheret, M. Yaniv, Unité des Virus Oncogènes).

5- Use of radioimagers (Beta-imager and Microimager)

This technique allows the localization and quantification of radiolabelled molecules, on tissue sections. This is a sensitive technique which can be combined with the histological analysis. We have studied:

  1. the pharmacodistribution of HB-19 (a pentameric pseudopeptide against VIH) on the whole body sections of rat. Collaboration with B. Krust, A. Hovanessian, unité de Virologie et Immunologie Cellulaire ; C. Rougeot, Unité de Génétique et Biochimie du développement, R. Vienet, JM Grognet, CEA

  2. the in vivo localisation of Entamoeba histolytica in the model of hepatic amebiasis. M.C. Rigothier (Faculté de Pharmacie de Chatenay-Malabry) and N. Guillen (Unité de Biologie Cellulaire du Parasitisme)

  3. The in vivo distribution of radiolabelled IgA immunoglobulins, specific of Shigella in nasopharynx and lung sections. Coll. Ph. Sansonetti, A. Phalipon (Unité de Pathogénie Microbienne des Muqueuses)



  publications

puce Publications of the unit on Pasteur's references database


  personnel

  Office staff Researchers Scientific trainees Other personnel
 

Alonso Françoise, falonso@pasteur.fr

Huerre Michel, mhuerre@pasteur.fr

Fiette Laurence, lfiette@pasteur.fr

Elies Laetitia, . eliesl@pasteur.fr

Avé Patrick, pave@pasteur.fr

Cardona Ana, cardona@pasteur.fr

Chimy Marie Christine, mcchimy@pasteur.fr

Khun Huot, hkhun@pasteur.fr

Maurin Sabine, smaurin@pasteur.fr

Tanguy Myriam, mtanguy@pasteur.fr

Wuscher Nicole, nwuscher@pasteur.fr


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