Unit: Histopathology

Director: Michel Huerre

The Histotechnology and Pathology unit is part of the department of Microbial pathogenesis that studies bacterial (Mycobacteria, Bordetella, Neisseria) and viral (Herpes virus) infections and parasitic diseases (Leishmania, Entamoeba, Aspergillus) using animal models. Our unit also studies the timing of recruitment of the inflammatory cells (particularly the dendritic cells) in response to different types, of infectious agents. In addition, we are investigating the roles of the Hnf1 transcription factor and the Snf5 and Plag genes during oncogenesis by analysing the phenotypes of genetically modified mouse cell lines. Also, our laboratory has developed a technique that uses a Beta-imager for quantitative autoradiography on tissue or whole body sections. I-Infectious diseases (human and experimental)

1-1 Mycobacteria. Mycobacteria are a large and ubiquitous group of pathogens which cause chronic granulomatous lesions when they persist within phagocytic cells (Macrophages, dendritic cells). The histological spectrum can be defined as bipolar: histiocytic or granulomatous. We have used various experimental models to define typical host cell reactions, which vary according to the genotype (mutant strains, BCG, rd1 strains) of the infectious agent and have different time courses of response. We have also investigated other bacterial models with respiratory tropism: Bordetella persists within the host and on day two specifically recruits dendritic cells. If a previous viral infection has occurred (i.e. Myxovirus), Neisseria can diffuse within the respiratory tract and lungs and induce local and general immunosuppression.

1-2 Helicobacter (Hp) and gastric pathology (Coll A. Labigne, R. Ferrero and E. Touati, UPBM). We have investigated the chronic gastritis induced by Hp and the mutagenic effects on the gastric epithelium in a transgenic mouse cell line (strain: Big Blue I Lac I). Induction of the mutagenic effects and the amount of local NO production correlate with the development and severity of the gastritis and with the occurrence of metaplasia (considered as precancerous lesions). Neither dysplasia lesions nor carcinomas were observed.

1-3 Gram positive: Listeria model (Coll M. Lecuit and P. Cossart). The mechanism used by Listeria to cross the digestive barrier was studied in the unit of P. Cossart. The morphological study was conducted in our laboratory using a transgenic animal model that produces E-cadherin. In parallel, we studied a number of other human pathologies, particularly placentitis.

1-4 Virus: Kaposi's disease and the HHV8 model (Coll A. Gessain, Oumkaltoum Hbid, I.P. Marocco). Kaposi's disease is an unusual form of vascular neoplasm believed to be caused by HHV8 (see photo). We investigated several strains isolated from distinct geographical areas (Russia, Africa, Oceania). Immunohistochemical studies found the virus in spindle cells. The clonality of the virus has been studied in the lab of A. Gessain.

II Phenotypic analysis of genetically modified mouse cell lines (Coll. L. Gresh, M. Yaniv, Unité d'Expression génétique et maladies)

We have studied the role of HNF1b in the embryonic development of the liver and kidney using murine strains in which this gene has been inactivated. Our Unit has studied murine models of salivary gland and breast tumours. These types of tumours are associated with the over-expression of the Plag oncogene (Coll. I. Van Valckenborgh, M. Chavez, Centre for human genetics, KUL, Louvain).

III Quantitative autoradiography (A. Cardona)

The unit has developed several applications for quantitative autoradiography using a Beta-imager combined with pathological studies. We have used this technique to study the distribution of isatin within the rat brain and to locate the nicotine, cystine, epibatidine and bungarotoxin binding sites within the brain of Macaca Mulatta. (Coll. J.P. Changeux, Unit of receptors and cognition).

Keywords: Pathology, histopathology, Infectious diseases, pathogenesis, beta-imager


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