Microsporidia are obligate intracellular protozoan parasites which cause wide variety of opportunistic infections in AIDS patients. The most common microsporidium associated with AIDS, Enterocytozoon beneusi, causes chronic diarrhea in the HIV-infected individuals. However, an animal model for E. beneusi is not available at present. Most of the experimental studies on microsporidia have been carried out on with Encephalitozoon cuniculi. This microsporidium, which commonly infects rodents, has been reported in humans as well. Several reports of disseminated E. cuniculi infection in HIV-infected patients have appeared recently. E. cuniculi is also very closely related to other microsporidia like Encephalitozoon hellum and Encephalitozoon intestinalis, which are also known to cause complications in AIDS individuals. Very little is known about the immune mechanisms against microsporidial infection in the normal host. The cellular immunity appears to be important for protection against an E. cuniculi challenge. Preliminary studies suggest that CD8+ T cells are an essential component of the immune response. Therefore, the detailed analysis of CD8+ T cell immunity is essential for understanding the immunoprotective mechanism against E. cuniculi infection. The first specific aim in this project will be to evaluate the kinetics of CD8+ T cell response during the course of E. cuniculi infection. The difference in this response between the resistant and susceptible species of mice will be determined and compared; the cytotoxic activity of the CD8+ T cells from the infected normal and immunocompromised animals will be assayed. The second specific aim is to determine the efficacy of the adoptive transfer of immune CD8+ T cells into infected immunocompromise host. Next, the length of time for which the immune CD8+ T cells can retain their activated/memory state in the naive immunocompromised host will be determined. In the third specific aim the role of gamma/delta T cells and the CD4+ T cells in the induction and maintenance of CD8+ T cell immunity will be evaluated. These studies will enable extrapolation to the immune mechanisms against other microsporidia, like E. beneusi, which is more frequently encountered by AIDS patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
7R01AI043693-04
Application #
6430449
Study Section
Special Emphasis Panel (ZRG5-ARRB (04))
Program Officer
Laughon, Barbara E
Project Start
1998-09-15
Project End
2002-08-31
Budget Start
2000-10-06
Budget End
2001-08-31
Support Year
4
Fiscal Year
2000
Total Cost
$145,265
Indirect Cost
Name
Louisiana State University Hsc New Orleans
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
Moretto, Magali M; Khan, Imtiaz A; Weiss, Louis M (2012) Gastrointestinal cell mediated immunity and the microsporidia. PLoS Pathog 8:e1002775
Moretto, Magali M; Lawlor, Elizabeth M; Khan, Imtiaz A (2010) Lack of interleukin-12 in p40-deficient mice leads to poor CD8+ T-cell immunity against Encephalitozoon cuniculi infection. Infect Immun 78:2505-11
Moretto, Magali M; Lawlor, Elizabeth M; Xu, Yanji et al. (2010) Purified PTP1 protein induces antigen-specific protective immunity against Encephalitozoon cuniculi. Microbes Infect 12:574-9
Lawlor, Elizabeth M; Moretto, Magali M; Khan, Imtiaz A (2010) Optimal CD8 T-cell response against Encephalitozoon cuniculi is mediated by Toll-like receptor 4 upregulation by dendritic cells. Infect Immun 78:3097-102
Moretto, Magali M; Lawlor, Elizabeth M; Khan, Imtiaz A (2008) Aging mice exhibit a functional defect in mucosal dendritic cell response against an intracellular pathogen. J Immunol 181:7977-84
Moretto, Magali M; Weiss, Louis M; Combe, Crescent L et al. (2007) IFN-gamma-producing dendritic cells are important for priming of gut intraepithelial lymphocyte response against intracellular parasitic infection. J Immunol 179:2485-92
Moretto, Magali; Weiss, Louis M; Khan, Imtiaz A (2004) Induction of a rapid and strong antigen-specific intraepithelial lymphocyte response during oral Encephalitozoon cuniculi infection. J Immunol 172:4402-9
Bacchi, Cyrus J; Weiss, Louis M; Lane, Schenella et al. (2002) Novel synthetic polyamines are effective in the treatment of experimental microsporidiosis, an opportunistic AIDS-associated infection. Antimicrob Agents Chemother 46:55-61
Moretto, M; Durell, B; Schwartzman, J D et al. (2001) Gamma delta T cell-deficient mice have a down-regulated CD8+ T cell immune response against Encephalitozoon cuniculi infection. J Immunol 166:7389-97
Moretto, M; Casciotti, L; Durell, B et al. (2000) Lack of CD4(+) T cells does not affect induction of CD8(+) T-cell immunity against Encephalitozoon cuniculi infection. Infect Immun 68:6223-32

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