Dr. Hesse has been an Assistant Professor in the Department of Microbiology
and Immunolgy since 2002. He received a diploma in biochemistry from the Free
University in Berlin, Germany in 1994. Then he joined the German Research Center
for Rheumatic Diseases (DRFZ) in Berlin, Germany, where he received his Ph.D.
from the Alexander v. Humboldt University, Berlin in 1997. Later he spent 5 years
at the National Institutes of Health in Bethesda, MD. He investigates the development
of chronic inflammation in a model of schistosomiasis.
Research Interests
| Graduate Fields | Lab
Members | Related Links | Selected
References
Research Interests
Chronic inflammation causes morbidity and mortality of a large number of
patients worldwide. These diseases are weakly curable and often lead to lifelong
treatments of patients, thereby adding a major economic burden. The further
investigation of mechanisms, which control immune responses, will improve our
understanding of inflammatory diseases and has the most promising potential
for more effective means of treatment.
Helminthic parasites cause long-lasting infectious diseases, often accompanied
by chronic inflammation. Their complicated life cycle requires a carefully orchestrated
interaction with their mammalian host. They have to avoid being destroyed by
the host's immune system, and they also have to keep their host alive
for relatively long time periods. Therefore, these infections constitute important
models to investigate immunoregulation under conditions of chronic infection
and inflammation. In schistosomiasis, a major tropical disease resulting from
persistent infection with trematodes, female worms lay up to several hundred
eggs daily for several years, most of which leave the host body. Significant
numbers of eggs get accidentally trapped and induce vigorous local inflammatory
responses. Numerous studies in mice and humans have demonstrated the importance
of the egg-induced host T helper cell cytokine response for survival and pathology
in acute and chronic schistosomiasis. This cytokine response is carefully controlled.
Failure to establish or maintain a balanced immune response against parasite
eggs has severe consequences for the host.
We investigate the role of immunosuppressive regulatory T cells as a potential
regulatory mechanism in schistosomiasis. Our data demonstrate that CD4+Foxp3+
naturally-occurring regulatory T cells (naTreg) prevent exacerbated Th-2 cytokine
responses in our model. Recent data indicate that many naTregs change to an
active/memory phenotype when the disease progresses to chronic inflammation.
We speculate that these cells are particularly important to control and maintain
a balanced response in chronic schistosomiasis. We also explore whether these
activated naTregs are able to crossregulate unrelated inflammatory responses
in infected hosts. These results could explain the negative correlation between
helminthic infections and allergic diseases. We expect that the results of this
research will improve our knowledge regarding the disease etiology of chronic
schistosomiasis and help to develop new treatment strategies for a variety of
chronic inflammatory diseases.
Graduate Fields
Lab Members
Related Links
Disease facts and current developments (http://www.who.int/topics/schistosomiasis/en/)
University of Cambridge Department of Pathology Schistosomiasis Research Group (http://www.path.cam.ac.uk/~schisto/home-page.html)
An overview of the disease and some biology of the parasite:
Ross, A. G., Bartley, P. B., Sleigh, A. C., Olds, G. R., Li, Y., Williams, G. M., McManus, D. P.(2002). "Schistosomiasis." NEngl J Med 346:1212-20.
Selected References
Hesse, M., Cheever, A., W., Jankovic, D., Wynn, T. A. (2000). "NOS-2 mediates the protective anti-inflammatory and antifibrotic effects of the Th1-inducing adjuvant, IL-12, in a Th2 model of granulomatous disease." Am J Pathol 157:945-955.
Hesse, M., Modolell, M., La Flamme, A. C., Schito, M., Fuentes, J. M., Cheever, A. W., Pearce, E. J., Wynn, T. A.(2001). "Differential regulation of nitric oxide synthase-2 and arginase-1 by type 1/type 2 cytokines in vivo: granulomatous pathology is shaped by the pattern of L-arginine metabolism." J Immunol 167:6533-44.
Hoffmann, K. F., McCarty, T. C., Segal, D. H., Chiaramonte,, M.Hesse, Davis, E. M., Cheever, A., W.Meltzer, P. S., Morse, H. C., 3rd, Wynn, T. A. (2001). "Disease fingerprinting with cDNA microarrays reveals distinct gene expression profiles in lethal type 1 and type 2 cytokine-mediated inflammatory reactions." Faseb J 15:2545-7.
Hesse, M., C. A. Piccirillo, Y. Belkaid, J. Prufer, M. Mentink-Kane, M. Leusink, A. W. Cheever, E. M. Shevach, and T. A. Wynn. (2004). The pathogenesis of schistosomiasis is controlled by cooperating IL-10-producing innate effector and regulatory T cells. J Immunol 172:3157-3166.
Kaviratne, M., M. Hesse, M. Leusink, A. W. Cheever, S. J. Davies, J. H. McKerrow, L. M. Wakefield, J. J. Letterio, and T. A. Wynn. (2004). IL-13 activates a mechanism of tissue fibrosis that is completely TGF-beta independent. J Immunol 173:4020-4029.
