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
E-mail:
nberkova@vet-alfort.fr
Abstract:
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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