报告题目：Immunoregulation by intestinal helminthes
报 告 人：Hai Ning Shi, DVM, PhD （哈佛医学院粘膜免疫实验室）
报告时间：2011年11月9日（星期三）8:30-10:00
报告地点：雅安校区育新楼（十教）一楼的报告厅
组织单位：动物医学院 （教育部创新团队教授学术论坛）
欢迎广大师生参加！
Hai Ning Shi简介（至2008年）
Education:
1982 D.V.M. Department of Veterinary Medicine, Qinghai University, School of Animal Science and Veterinary Medicine, China
1996 Ph.D. Institute of Parasitology, McGill University, Montreal, Canada
Postdoctoral Training:
1996-1999 Postdoctoral Fellow, Mucosal Immunology Laboratory, Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital and Harvard Medical School
Narrative Report:
My research interests are focused on mucosal immunology and intestinal inflammation. Our ongoing research studies microbial pathogenesis and immune regulation of intestinal inflammation using helminth infection model. We study immunomodulatory effects of intestinal helminthes on mucosal immunity. We are particularly interested in exploring the mechanisms by which the helminth parasite modulates intestinal mucosal response to enteric bacteria and bacteria-associated and immune-mediated intestinal inflammation using helminth co-infection model system. Evidence from epidemiological studies indicates an inverse correlation between exposure to helminthes and the incidence of certain immune-mediated diseases (the hygiene hypothesis), including inflammatory bowel diseases (IBD). Helminth infection has been known to dampen Th1 reactions to other infections. Thus, due to the ability to attenuate damaging Th1 driven inflammatory responses in the host, helminthes have been proposed and tested as a therapeutic agent for the treatment of certain immune-mediated diseases, including IBD. However, recent experimental results, including our own, provide evidence to indicate that intestinal helminth infection can also exacerbate both infectious and non-infectious forms of colitis under some circumstances. A more comprehensive understanding of the mechanisms by which these parasites alter host intestinal inflammatory and immune responses may provide new information for establishing more effective and safer preventive and therapeutic approaches to the treatment of both Th1 and Th2-mediated diseases, and for the design of effective intestinal vaccines.
We also study the impact of intestinal colonization of probiotics at early life on the development and regulation of mucosal T cell responses (Th1, Th2, Th17 and Treg) and explore the mechanisms by which probiotics modulate mucosal immunity and host protection against enteric pathogens. We also explore the role of bacterial products as triggering agents to alter intestinal barrier function and mucosal immune function. Our research will provide greater insight about how intestinal microorganisms may alter the regulatory mechanisms of mucosal immunity, which may be instrumental in the establishment of effective preventive and therapeutic approaches for the treatment of immune mediated disorders.
Original Articles
1. Shi HN, Scott ME, Stevenson MM, Koski KG. Zinc deficiency impairs T cell function in mice with primary infection of Heligmosomoides polygyrus (Nematoda). Parasite Immunology. 1994: 16: 339-350.
2. Hai Ning Shi, Marilyn E. Scott, Kristine G. Koski, Marjolaine Bouley and Mary M. Stevenson. Energy restriction and severe zinc deficiency influence development, survival and reproduction of Heligmosomoides polygyrus (Nematoda) during primary and challenge infections in mice. Parasitology . 1995; 110: 599-609.
3. Hai Ning Shi, Kristine G. Koski, Mary M. Stevenson and Marilyn E. Scott. Zinc deficiency and energy restriction modify immune responses in mice during both primary and challenge infection with Heligmosomoides polygyrus (Nematoda). Parasite Immunology. 1997;19: 363-373.
4. Hai Ning Shi, Marilyn E. Scott, Kristine G. Koski and Mary M. Stevenson. Zinc deficiency and concurrent energy restriction reduce the functions of murine T cells and antigen-presenting cells during a gastrointestinal nematode infection. Journal of Nutrition. 1997; 128: 20-27.
5.Hai Ning Shi, Christian Ingui, Ingrid Dodge and Cathryn Nagler-Anderson. A helminth induced mucosal Th2 response alters non-responsiveness to oral administration of a soluble antigen. Journal of Immunology. 1998, 160: 2449-2455.
6. Hai Ning Shi, Michael J. Grusby and Cathryn Nagler-Anderson. Orally induced peripheral nonresponsiveness is maintained in the absence of functional Th1 or Th2 cells. Journal of Immunology. 1999, 162; 5143-5148.
7. James G. Fox, Paul Beck, Charles A Dangler, Mark T. Whary, Timothy C. Wang, Hai Ning Shi and Cathryn Nagler-Anderson. Concurrent enteric infection modulates inflammation, gastric immune responses, and reduces helicobacter-induced gastric atrophy. Nature Medicine. 2000; 6 (45): 536-542.
8. Hai Ning Shi, Hao Yuan Liu and Cathryn Nagler-Anderson. Enteric infection acts as an adjuvant for the response to a model food antigen. Journal of Immunology. 2000, 165:6174-6182.
9. Bashir ME, Andersen P, Fuss IJ, Shi HN, Nagler-Anderson C. An enteric helminth infection protects against an allergic response to dietary antigen. Journal of Immunology . 2002, 169(6):3284-3292.
10. Bashir MEH, Louie S., Shi H.N. and Nagler-Anderson C. TLR4 signaling by intestinal microbes influences susceptibility to food allergy. 2004. Journal of Immunology. 172(11): 6978-87.
11. Moran ST, Cariappa A, Liu H, Boboila C, Shi HN, Holland PM, Peschon JJ, Pillai S. Protein kinase C-associated kinase is not required for the development of peripheral B lymphocyte populations. Mol Immunol. 2005.
12. Annaiah Cariappa, Irina B. Mazo, Catharine Chase, Hai Ning Shi, Haoyuan Liu, Qian Li, Harris Rose, Harry Leung, Bobby J. Cherayil, Paul Russell, Ulrich von Andrian, and Shiv Pillai. Perisinusoidal B Cells in the Bone Marrow Participate in T-Independent Responses to Blood-Borne Microbes. Immunity. 2005. 23 (4): 397-407.
13. Chien-Chang Chen, Steve Louie, Beth McCormick, Allan Walker and Hai Ning Shi. Concurrent infection of an intestinal helminth parasite impairs host resistance to enteric Citrobacter rodentium and enhances Citrobacter-induced colitis in mice. 2005. Infection and Immunity. 73 (9): 5468-5481.
14. Chien-Chang Chen, Hai Ning Shi and Allan Walker. Precolonization with the Probiotic Lactobacillus acidophilus early in life effectively inhibits murine Citrobacter rodentium colitis. Pediatric Research. 2005. 58 (6): 1185-1191.
15. Tor C. Savidge, Paul G. Newman, Wei-Hua Pan, Mei-Qian Weng, Hai Ning Shi, Beth A. McCormick, Andrea Quaroni, W. Allan Walker. Lipopolysaccharide-induced human enterocyte tolerance to cytokine-mediated interleukin-8 production may occur independently of TLR-4/MD-2 signalling. Pediatric Research . 2006. 59 (1): 85-95.
16. Chien-Chang Chen, Steve Louie, Beth McCormick, Allan Walker and Hai Ning Shi. Helminth primed dendritic cells alter the host response to enteric bacterial infection. The Journal of Immunology. 2006. 176: 472-483.
17. Wall, D.M, Nadeau, W.J, Pazos, M.A, Shi, H.N, Galyov, E.E, McCormick, B.A. Identification of the Salmonella enterica serotype Typhimurium SipA domain responsible for inducing neutrophil recruitment across the intestinal epithelium. Cellular Microbiology. 2007. 9(9): 2299-2313.
18. Harrington, Lynne; Srikanth, Chittur; Antony, Reuben; Shi, Hai Ning; Cherayil, Bobby. A role for natural killer cells in intestinal inflammation caused by infection with Salmonella enterica serovar Typhimurium. FEMS Immunol Med. Microbiol. 2007. 51: 372–380
19. Annaiah Cariappa, Cristian Boboila, Stewart T. Moran, Haoyuan Liu, Hai Ning Shi, and Shiv Pillai. The Recirculating B Cell Pool Contains Two Functionally Distinct, Long-Lived, Posttransitional, Follicular B Cell Populations. The Journal of Immunology. 2007. 179(4): 2270-2281.
20. Meiqian Weng, Deke Huntley, I-Fei Huang, Ondulla Foye-Jackson, Lijian Wang, Aliese Sarkissian, Qingping Zhou, W. Allan Walker, Bobby J. Cherayil and Hai Ning Shi . Alternatively activated macrophages in intestinal helminth infection: effects on concurrent bacterial colitis. The Journal of Immunology. 2007. 179:4721-4731.
21. Lynne Harrington, Chittur V. Srikanth, Reuben Antony, Sue J. Rhee, Andrew L. Mellor, Hai Ning Shi, and Bobby J. Cherayil. 2008. Deficiency of Indoleamine 2,3-Dioxygenase Enhances Commensal-Induced Antibody Responses and Protects against Citrobacter rodentium-Induced Colitis. Infection and Immunity . Vol. 76: 3045-3053.
22. Yasuyo Shimomura, Atsuhiro Ogawa, Mayumi Kawada, Ken Sugimoto, Emiko Mizoguchi, Hai-Ning Shi, Shiv Pillai, Atul K. Bhan, and Atsushi Mizoguchi. 2008. A unique B2 B cell subset in the intestine. The Journal of Experimental Medicine, Vol. 205, No. 6, 1343-1355.
23. Lijian Wang, Erin E. Johnson, Hai Ning Shi, W. Allan Walker, Marianne Wessling-Resnick, Bobby J. Cherayil. 2008. Attenuated inflammatory responses in hemochromatosis reveal a role for iron in the regulation of macrophage cytokine translation. The Journal of Immunology. 2008. 181 (4) 2723-2731.
24. Michael Pazos, Dario Siccardi, Karen L. Mumy, Jeffrey D. Bien, Steve Louie, Hai Ning Shi, Karsten Gronert, Randall J. Mrsny, and Beth A. McCormick. Multi-Drug Resistance Transporter 2 Regulates Mucosal Inflammation by Facilitating the Synthesis of Hepoxilin A3. The Journal of Immunology. 2008. In press
