Aged individuals experience increased morbidity and mortality from infectious diseases. This is especially evident in cases of emerging diseases such as SARS and West Nile Virus, where most of the patients that succumb to disease are over the age of 50. This increase in susceptibility is mediated by the age-related decline in immunity commonly referred to as "Immune senescence". Since the proportion of aged individuals is rapidly increasing, understanding the defects in the immune systems of this vulnerable population will undoubtedly help us design interventions to improve immunity and increase the efficacy of vaccinations. The emphasis of my laboratory is to further our understanding of mechanisms underlying age-related T cell immune deficiencies using nonhuman primate animal models. More specifically work in my laboratory is focused on three areas:
1. Elucidating immunological deficiencies that underlie varicella zoster virus (VZV) reactivation
2. Understanding the interplay between menopause and immunity in aged women
3. Determining how diet modulates immune senescence.
VZV reactivation and herpes zoster:
The reactivation of varicella zoster virus (VZV) results in herpes zoster, more commonly known as shingles, which causes significant morbidity and sometimes mortality in the elderly. The immunological and virological bases for VZV reactivation are poorly understood. Furthermore, the currently available vaccines against VZV are not very efficacious. We have developed the first nonhuman primate animal model that recapitulates hallmarks of VZV infection in humans. We are using this animal model to identify aspects of immune senescence that contribute to herpes zoster. Furthermore, we are characterizing the pattern of viral gene expression to identify viral genes that can either be used in subunit vaccines against herpes zoster, or be deleted to create a safer attenuated vaccine.
Ovarian senescence and its impact on immunity:
Due to increasing life expectancy, women in the United States can expect to live about one third of their life after menopause. However, despite intense research, we do not fully understand the impact of menopause on immune senescence. Several studies have shown that female sex hormones modulate immune function in women. More recently, we have shown that surgical menopause results in diminished immune response to vaccination and that estradiol alone or in combination with progesterone can improve immune responsiveness in surgically post- menopausal aged female rhesus macaques. Research in the lab is focused on understanding the mechanisms underlying the effects of menopause and different hormone therapy regimens on immune function in adult and middle-aged female rhesus macaques in collaboration with Drs. Urbanski and Kohama.
Modulation of immune senescence by diet:
Abnormalities in immune function are likely to be associated with, or even the cause of, obesity- and alcoholism-related diseases. However, the relationship between metabolism and immunity is poorly understood. Recently, together with Drs. Grove, Grant and Neuringer's laboratories, we are investigating how the consumption of a diet high in fat and sugars, excessive intake of alcohol and the composition of essential fatty acids, respectively, affect the aging of the immune system.
Dr. Ilhem Messaoudi is an assistant scientist at the center and at the Vaccine and Gene Therapy Institute, OHSU. She received her B.Sc. in Biochemistry from Lafayette College (Easton, Pennsylvania) in 1996. She obtained a joint doctorate degree in immunology from The Weill Graduate School of Medical Sciences of Cornell University and Memorial Sloan-Kettering Cancer Center in 2001. During her graduate tenure, she studied factors that influence the efficacy of the CD8 T cell response to viral infection. Dr. Messaoudi carried out her post-doctoral training in Dr. Janko Nikolich-Zugich's laboratory at Oregon Health & Science University, Oregon National Primate Research Center, where she focused on the characterization of changes in the phenotype and function of T cells with age in both mice and nonhuman primates.
Dr. Messaoudi serves on the Executive Committee of the Healthy Aging Alliance.
Messaoudi I., Warner J., Fischer M., Park B., Hill B., Mattison J., Lane M. A., Roth G. S., Ingram D. K., Picker L. J., Douek D. C., Mori M., and Nikolich-Zugich J. (2006) Delay of T cell senescence by caloric restriction in aged long-lived non-human primates. Proc Natl Acad Sci US. 103(51):19448-53.
Messaoudi I, Fischer M.B., Warner J., Park B., Mattison J., Ingram D.K., Totonchy T., Mori M., and Nikolich-Zugich J. (2008) Optimal window of caloric restriction onset limits its beneficial impact upon T cell senescence in primates. Aging Cell 7(6):908-19.
Messaoudi I., Barron A., Wellish M., Engelmann F., Legasse A., Planer S., Gilden D., Nikolich-Zugich J., and Mahalingam R. (2009) Simian varicella virus infection of Rhesus macaques recapitulates essential features of varicella zoster virus infection in humans. PLoS Pathogen 5(11):e1000657.
Haberthur K., Engelmann F., and Messaoudi I. (2010) Immune senescence in aged rhesus macaques. J Exp Geron 45(9):655-61.
Engelmann F., Barron A., Neuringer M., Urbanski H., Kohama S., and Messaoudi I. (2010) Surgical menopause accelerates immune senescence and reduced immune response to vaccination. AGE 33(3):275-89
Haberthur K., Engelmann F., Barron A., LegasseA., DewaneJ., FischerM., KernsA., BrownM., and MessaoudiI. (2011) A critical role for CD4 T cells in a nonhuman primate model of VZV infection. Accepted PLoS Pathogens
Meyer C., KernsA., Barron A., Kreklywich C., Streblow D., and MessaoudiI. (2011) Simian varicella virus gene expression during acute and latent infection of Rhesus macaques. Accepted Journal of Neurovirology