|
|
 |
BIOGRAPHY:
Dr. Nedospasov is Professor and Head of the Laboratory of Molecular Immunology at both, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, in Moscow and A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University. He received his Ph.D. and his D.Sc. from the Institute of Molecular Biology. He has conducted research in the Departments of Nucleic Acid Biosynthesis of the Institute of Molecular Biology as a Junior Staff Scientist, Senior Investigator, and as Head of the Cytokine Molecular Biology Group. He has been a visiting scientist in the Department of Virology of the Swiss Institute for Experimental Cancer Research in Lausanne and at the NCI-Frederick Cancer Research and Development Center in Frederick, Maryland. Dr. Nedospasov was first named an HHMI International Research Scholar in 1995. His HHMI project is entitled "Distinct Role of TNF Produced by Different Cell Types in Infectious Disease and Experimental Hepatitis."
RESEARCH ABSTRACT SUMMARY:
Distinct Role of TNF Produced by Different Cell Types in Infectious Disease and Experimental Hepatitis
To predict the outcome of continuous TNF blockage in human patients,
an analysis of the physiological consequences of partial or complete
TNF ablation is needed. At the previous meetings, we reported on
generation and characterization of mice with TNF ablation in distinct
types of cells, such as macrophages/neutrophils (M-TNF mice), T cells
(T-TNF mice), and B cells (B-TNF mice). We have now evaluated the mice
in three pathophysiological models; in two of these, TNF plays a
deleterious role, and in the third one, a protective role. M-TNF mice
are uniquely protected against acute LPS-D-Gal toxicity, consistent
with the fact that only these mice lack detectable serum TNF after LPS
injection. However, in ConA-induced hepatitis, both M-TNF and T-TNF
mice, but not B-TNF mice, show significant protection. In a Listeria
monocytogenes infection model, both M-TNF and T-TNF mice are
susceptible and show increased bacterial loads in organs, whereas with
the same parasite doses, both B-TNF and wild-type mice can effectively
control the infection. These findings suggest distinct roles for
macrophage-derived and T cell-derived TNF: both can be protective or
deleterious, depending on the physiological conditions that trigger TNF
production.
Photo: Kent Kallberg, Kallberg Studios
|
