This application proposes to analyze the cytokine response to Cryptosporidium infection in immunocompetent human hosts and people with AIDS. These investigators hypothesize that differential intestinal cytokine production accounts for the symptoms (and resolution of symptoms) in immunocompetent hosts, and the development of chronic infection in people with AIDS. The investigators propose that Cryptosporidium infection in immunocompetent hosts may be divided into three broad phases: injury, control, and healing.
The specific aims for this project include: 1) Identification and quantitation of mucosal cytokines during the injury phase of cryptosporidiosis in both normal volunteers and people with AIDS. 2) Identification and quantitation of mucosal cytokines during the control phase of cryptosporidiosis and correlation with oocyst excretion, CD4+ cell count, HIV viral load, stool volume, intestinal inflammation, and fecal anti-cryptosporidial IgA. 4) A trial of recombinant IL-12 as adjunctive therapy in chronic cryptosporidiosis in AIDS will be performed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI041735-03
Application #
2887543
Study Section
Special Emphasis Panel (ZRG5-ARRE (01))
Program Officer
Laughon, Barbara E
Project Start
1997-09-01
Project End
2001-09-29
Budget Start
1999-09-01
Budget End
2001-09-29
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
Chappell, Cynthia L; Darkoh, Charles; Shimmin, Lawrence et al. (2016) Fecal Indole as a Biomarker of Susceptibility to Cryptosporidium Infection. Infect Immun 84:2299-306
Preidis, Geoffrey A; Wang, Heuy-Ching; Lewis, Dorothy E et al. (2007) Seropositive human subjects produce interferon gamma after stimulation with recombinant Cryptosporidium hominis gp15. Am J Trop Med Hyg 77:583-5
Wang, Heuy-Ching; Dann, Sara M; Okhuysen, Pablo C et al. (2007) High levels of CXCL10 are produced by intestinal epithelial cells in AIDS patients with active cryptosporidiosis but not after reconstitution of immunity. Infect Immun 75:481-7
Okhuysen, Pablo C; Chappell, Cynthia L; Lewis, Dorothy E et al. (2005) Treatment of chronic cryptosporidiosis in AIDS with rIL-12 induces an immune response associated with improvement but severe side-effects. AIDS 19:1333-4
Okhuysen, Pablo C; Rogers, G Aaron; Crisanti, Andrea et al. (2004) Antibody response of healthy adults to recombinant thrombospondin-related adhesive protein of cryptosporidium 1 after experimental exposure to cryptosporidium oocysts. Clin Diagn Lab Immunol 11:235-8
Stringer, Janet L; Marks, LaToia M; White Jr, A Clinton et al. (2003) Epileptogenic activity of granulomas associated with murine cysticercosis. Exp Neurol 183:532-6
White Jr, A Clinton; Robinson, Prema; Okhuysen, Pablo C (2003) Human studies provide insight into the pathogenesis, immunology, and treatment of cryptosporidiosis. Clin Infect Dis 37:989; author reply 989-90
Robinson, Prema; Okhuysen, Pablo C; Chappell, Cynthia L et al. (2003) Substance P expression correlates with severity of diarrhea in cryptosporidiosis. J Infect Dis 188:290-6
Alcantara, Cirle S; Yang, Chang-Hun; Steiner, Theodore S et al. (2003) Interleukin-8, tumor necrosis factor-alpha, and lactoferrin in immunocompetent hosts with experimental and Brazilian children with acquired cryptosporidiosis. Am J Trop Med Hyg 68:325-8
Okhuysen, Pablo C; Rich, Stephen M; Chappell, Cynthia L et al. (2002) Infectivity of a Cryptosporidium parvum isolate of cervine origin for healthy adults and interferon-gamma knockout mice. J Infect Dis 185:1320-5

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