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The African enigma: the parasite's perspective
  1. J G FOX
  1. Division of Comparative Medicine
  2. Massachusetts Institute of Technology
  3. 77 Massachusetts Ave
  4. Bldg. 16-825C, Cambridge, MA 02139, USA
  5. Division of Gastroenterology
  6. University of Massachusetts Medical Center
  7. Biotech 2, Suite 202, 373 Plantation St
  8. Worcester, MA 01605-2377, USA
  9. Mucosal Immunology Laboratory
  10. Massachusetts General Hospital East
  11. Building 149, 13th Street, Charlestown, MA 02129, USA
  1. JG Fox. jgfox{at}mit.edu
  1. T C WANG
  1. Division of Comparative Medicine
  2. Massachusetts Institute of Technology
  3. 77 Massachusetts Ave
  4. Bldg. 16-825C, Cambridge, MA 02139, USA
  5. Division of Gastroenterology
  6. University of Massachusetts Medical Center
  7. Biotech 2, Suite 202, 373 Plantation St
  8. Worcester, MA 01605-2377, USA
  9. Mucosal Immunology Laboratory
  10. Massachusetts General Hospital East
  11. Building 149, 13th Street, Charlestown, MA 02129, USA
  1. JG Fox. jgfox{at}mit.edu
  1. C NAGLER-ANDERSON
  1. Division of Comparative Medicine
  2. Massachusetts Institute of Technology
  3. 77 Massachusetts Ave
  4. Bldg. 16-825C, Cambridge, MA 02139, USA
  5. Division of Gastroenterology
  6. University of Massachusetts Medical Center
  7. Biotech 2, Suite 202, 373 Plantation St
  8. Worcester, MA 01605-2377, USA
  9. Mucosal Immunology Laboratory
  10. Massachusetts General Hospital East
  11. Building 149, 13th Street, Charlestown, MA 02129, USA
  1. JG Fox. jgfox{at}mit.edu

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Editor,—We would like to thank Professor MacDonald for his interest in our work, and for his recent comment on our paper (

). However, we must take issue with a number of his comments.

With respect to the clinical implications of our study,1 we have not advocated treatment ofHelicobacter pylori infected patients with intestinal parasites for the purpose of inducing a shift in the Th1/Th2 immune response, a possibility raised by Professor MacDonald. As Professor MacDonald is well aware, this approach has been suggested for a number of chronic diseases such as inflammatory bowel disease. However, in the case of chronic H pylori infection, antibiotic therapy has proved effective and in our opinion is a much safer and more palatable approach for most patients.

We appreciate Professor MacDonald's careful analysis of our histopathological results. However, we are confused regarding his comments of “negative points” that were not sufficiently emphasised. The main findings in our study were thatH polygyrus coinfection attenuated the degree of parietal cell loss, mucous cell hyperplasia, and metaplasia, and resulted in an increase in bacterial colonisation. The changes in inflammation, as graded histologically, were clearly less marked. These latter findings simply underscore the notion that it is the T helper type of immune response rather than the overall severity or histological grade of inflammation that determines eventual epithelial injury. In addition, it is generally recognised that in theH felis mouse model, there is some degree of variability with respect to the degree of inflammatory response, which is well illustrated by our data. It is puzzling that Professor MacDonald would equate this biological variation with a problem regarding the “quality of the data”.

Further questions were raised regarding the conclusion thatH polygyrus infection biased the immune response to H felis along the same pathway. Our data clearly show that Th1 immune responses were decreased and Th2 immune responses were increased, and this was supported not only by cytokine profiles but also by H felisspecific humoral responses. We agree that this immunomodulatory effect may not be true for every intestinal parasite. However, as pointed out in our paper, other parasites such as Schistosoma mansoni have also been shown to induce polarised Th2 responses and downregulate intestinal Th1 responses. The question that Professor MacDonald raises regarding the specificity of the Th2 response forH felis (as opposed to H polygyrus) is an interesting one. However, the explanation that the increased Th2 cytokines in the stomach of mice infected with both H felisand H polygyrus are derived from “migration into the inflamed gastric mucosa of Th2 cells responding to H polygyrusantigens” seems less likely in our opinion.

We would agree that induction of a Th2 anti-H felis response may not be desirable in every instance. However, this comment again seems to miss the point. Data from numerous animal models have shown that a reduction in mucosal Th1 response together with upregulation of a mucosal Th2 response is associated with decreased progression to gastric atrophy and preneoplasia, and taken in this context, a Th2 polarised response is clearly a desirable outcome. Data from a number of laboratories have suggested that increased bacterial colonisation by itself does not lead to adverse consequences; in fact, in most mouse models the level of bacterial colonisation was inversely related to the degree of atrophy and metaplasia. It is our contention that a decreased Th1 response associated with a high rate of gastric colonisation is highly preferable to a strong Th1 response associated with decreased Helicobactercolonisation.

Finally, we concluded from our study that the ability of a concurrent helminth infection to ameliorateHelicobacter spp. induced gastric disease might partially explain the African enigma. It is clear that intestinal helminth infections are common in Africa, and also that there is marked variation in the pattern of helminth infections from continent to continent. The review by Professor MacDonald, aside from contributing insightful commentary on the topography of Africa and South America, has not provided additional information regarding the variable patterns and types of helminth infections in the two continents. Recent data from Mitchell and colleagues2 have supported the hypothesis that a Th2 polarised response to H pylori is more common in Africa while a Th1 polarised response is more common in Europe and Australia. We would suggest that further investigations of intestinal helminths, as well as host genetics,3 should be considered to account for this different pattern of immune response to H pylori, as well as the differing rates of gastric cancer induction.

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