Plenary Lecture

Plenary Lecture

Invasion of the Host Epithelium by the Microorganisms: Good or Bad News for the Host?

Dr. Nadia Nadejda Berkova
Senior Research Fellow, INRA
(French National Institute of Agriculture Research)
Laboratory of Mycoses, UMR 956, Jouy-en-Josas Research Centre
Maisons-Alfort, France

The host epithelium has permanent contact with the environment and a multitude of diverse microorganisms, resulting in a network of the host's defense mechanisms. Pathogens use various strategies to invade epithelial barriers, to hijack eukaryotic host function to their own benefit and use the epithelium as a reservoir for dissemination throughout the host. Alteration of the host cell apoptosis, promotion of cell proliferation or conversely, inhibition of cell growth and modulation of the cell differentiation by blocking of cell cycle progression are some of them. The mechanisms all of the stratagems employed by the pathogens are not fully elucidated, but they can contribute to the virulence of those microorganisms. However, the latest investigation of the interaction between host epithelium and microorganisms suggest that the epithelium is not a simple mechanical barrier: epithelial cells recognize microorganisms and initiate appropriate signaling which contribute to the endocytosis of microorganisms. It appears that capture of microorganisms by the epithelial cells is selective and that the different endocytic mechanisms may be enhanced by proinflammatory cytokines. The specificity of the recognition is illustrated by the various studies, showing that the epithelial cells distinguish the different morphotypes of the microorganisms. Using the model of the infection of respiratory epithelium by opportunistic pathogen Aspergillus fumigatus, we have shown that the airway epithelial cells identify the most invasive fungal form that may be beneficial for the host defense. Moreover, host epithelium exposed to the microorganisms, express various cytokines and different protective substances, such as antimicrobial peptides, with direct microbicidal or chemotactic activities, which might contribute to the regulation of host adaptive immunity against microbial invasion. Autocrine mechanismes of antimicrobial peptides expression was shown with the epithelial cells exposed to Aspergillus fumigatus. Further study of the regulation of antimicrobial peptides expression might provide the new approaches that may enhance its expression for potential therapeutic use.
Nevertheless, despite permanent exposure to a considerable amount of the microorganisms present in the environment, epithelium possesses the enormous capacity to keep its integrity, suggesting that some microbial strategies link to the mechanisms, which control the structural integrity of the tissue. Recent evidence supports the role of microbial factors in the maintenance of the integrity of the epithelial tissue: it was shown that Staphylococcus aureus as well as other microbial products induce epithelial repair, survival and growth and that such compensatory epithelial responses are mediated by autonomous non-inflammatory pathway. Therefore the outcome of the interaction between the host epithelium and microorganisms depends on multiple features.

Brief Biography of the Speaker:
Research interest focuses on the molecular understanding of immunological pathways and analysis of gene expression in the context of immune deregulation of the organism.
1990- PhD thesis in the Institute of Bioorganic Chemistry, Moscow, Russian Federation and Max-Delbruck Cancer Centre, Berlin-Buch, Germany. The thesis was related to the structure-functional analysis of Tumor Necrosis Factor. Part of the work was linked to the establishment of the new approach for the development of anti-cancer drugs using bispecific monoclonal antibody.
1991-1993-Post-doctoral training in Cancerology laboratory of Laval University, Quebec. The topic of study was related to investigation of the mechanisms of TNF action on the cancer cells.
1993-1995-Wyeth-Ayerst fellow in human reproduction, laboratory of endocrinology, St-Francois d'Assise Hospital, Quebec. The work was focused on the investigation of the physiopathology of endometriosis, followed by the finding of the important role of the haptoglobin in infertile patients with endometriosis.
1995-1997- Associate Professor at the medical faculty, Laval University, Quebec and a FRSQ (Quebec Medical Research Fondation) fellowship. The investigation of the team was devoted to the study of the cytokine-cells interaction in acute inflammatory response.
1998-2002- Invited scientist in Genetic and Development Unit, CNRS (French National Centre for Scientific Research) at Rennes University. Scientific projects related to the study of the mechanisms of the regulation of protein synthesis as well as to the development of the new methods for gene mapping.
2002-present-Senior Research Fellow, INRA (French National Institute of Agriculture Research), Maisons-Alfort, UMR 956, Mycology laboratory, head of the team. The current scientific interest focussed on molecular understanding of immunological pathways, immunogenetics and analysis of gene expression in the context of fungi-induced host immune disturbances and the development of animal models of infection to enhance the knowledge of immune deregulation of infected host.
The results of the research were published in peer-reviewed journals, book chapters and granted numerous international patents.
Reviewer for journals related to the field of immunology, reproduction and cell biology (Biology of reproduction, Human reproduction, The European Journal of Obstetrics & Gynecology and Reproductive Biology, FEBS letter, Clinical Immunology), an editorial board member for “ Dermatology” and some book series.
Invited speaker at numerous international meetings/workshops/seminars.

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