Immunology
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Cathryn Nagler

Associate Professor

Center for Immunology and Inflammatory Diseases
Division of Rheumatology, Allergy and Immunology
Massachusetts General Hospital
Building 149, 13th Street Room 6221
Charlestown, MA 02129-4404
Tel: 617-726-4161
Fax: 617-726-5651
email: cnagler@partners.org

 Cathryn Nagler

How does the gut associated lymphoid tissue distinguish innocuous dietary antigens and commensal bacteria from pathogenic microbes and mount an appropriate response to each?This is the central question being addressed in the Nagler laboratory.

In one approach to gain insight into the mechanisms regulating non-responsiveness to dietary antigen we are examining the consequences of mucosal immune system activation induced by enteric infection. Common chronic enteric helminthic or bacterial infections can act as adjuvants to prime for a response to otherwise tolerogenic forms of dietary antigen. One project focuses on understanding the basis for this adjuvant effect and the concomitant induction of microbially induced immunoregulatory mediators. We are also examining the effects of both Th1 and Th2 polarizing enteric infections on the response to oral vaccines. Although chronic enteric infection is endemic in much of the developing world, surprisingly little has been done to examine its influence on vaccine efficacy.

When the complex mechanisms governing non-responsiveness are perturbed, both Th2 biased (manifest as food allergy) and Th1 biased (manifest as inflammatory bowel disease) responses to the luminal contents ensue. It is becoming clear that we exist in a symbiotic relationship with the billions of bacteria that comprise the commensal flora. Healthy individuals don’t mount an immune response to their flora and yet receive potent flora derived signals that play a central role in the development of both the peripheral and mucosal immune systems. In recent work we have shown that the commensal flora induces immunoregulatory dendritic cells and T cells that are important for the prevention of hyperreactivity. A second project explores flora-induced immunoregulation at both the cellular and molecular level.

Finally we have expressed the gene for a model dietary antigen (OVA) under the control of an anaerobically inducible promoter for oral administration in a Salmonella vaccine construct. We are comparing the presentation of this immunogenic form of antigen to that of a tolerogenic form of antigen (OVA-FITC) (both administered orally) and examining the role of innate immune systemsignaling in governing decisions controlling tolerance and immunity.

 

Papers & Publications:

  1. Bashir, M.E.H., Andersen, P., Fuss, I.J., Shi, H.N. and C. Nagler-Anderson (2002). An enteric helminth infection protects against an allergic response to dietary antigen. J. Immunol. 169: 3284-3292.
  2. Bashir, M.E.H., Louie, S., Shi, H.N. and C. Nagler-Anderson (2004). TLR-4 signaling by intestinal microbes influences susceptibility to food allergy. J.Immunol. 172,6978-6987.
  3. Smith, D.W. and C. Nagler-Anderson (2005). Preventing intolerance: the induction of non-responsiveness to dietary and microbial antigens in the intestinal mucosal.J. Immunol., 174: 3851-3857.
  4. Prioult, G. and C. Nagler-Anderson (2005). Mucosal Immunity and allergic responses: lack of regulation and/or lack of microbial stimulation. Immunological. Review 206 Mucosal Immunuty Mayer, L. Ed. Blackwell Munksgaard Press, 204-218