IMMUNOLOGY AND CELL BIOLOGY OF THE INTERACTION BETWEEN LEISHMANIA PARASITES AND MACROPHAGES

We have focused upon the initiation of a Th1 response to the protozoan parasite, Leishmania major. Leishmania species are a significant cause of infectious disease in many tropical countries. Experimental infection of mice with L. major is a well-characterized and highly reproducible model of leishmaniasis. IL-12 is produced after infection with L. major and is necessary for the development of an appropriate Th1 response, but the source of IL-12 during L. major infection is unknown. While investigating the presentation of L. major antigens to naive transgenic T cells, we discovered that naive T cells can induce macrophages to secrete IL-12. Interestingly, the antigen dose required for T cell induction of IL-12 was lower than that required for stimulation of the T cells. 

We propose to investigate this potential source of IL-12 further. Our primary hypothesis is that the ability of naive T cells to induce IL-12 at low antigen doses is unique to macrophages. The first two specific aims address this hypothesis by (1) testing whether another model transgenic T cell is capable of inducing IL-12 from macrophages during antigen presentation; and by (2) testing whether dendritic cells can be induced by naive T cells to produce IL-12 at nonstimulatory doses of antigen. In the third specific aim we address the mechanism by which naive T cells induce IL-12, specifically whether CD40-CD40L interactions are necessary. Finally, we propose experiments which may identify innate cofactors that modulate this ability of naive T cells to induce IL-12. 

Because macrophages may be the first phagocytes to present antigens to T cells, this interaction may reinforce innate responses to infection and influence the course of the developing adaptive response.

Project technician Leslie Sayles working in Dr. Swier's lab.

Recent Publications and Presentations

Castro, R., K Scott, T. Jordan, B. Evans, J. Craig, E. L. Peters, and K. Swier.  2006.  The ultrastructure of the parasitophrous vacuole formed by Leishmania major.  J. Parasitol., 92(6):  1162-1170.

Sevilla, L. M., S. S. Comstock, K. Swier, and J. Miller.  2004.  Endoplasmic reticulum-associated degradation-induced dissociation of class II invariant chain complexes containing a glycosylation-deficient form of p41.  J. Immunol. 173:  2586-2593.

Presentations

K. Swier, T. Douglas, J. Bartley, S. Borum, L. Lewis, and L.J. Sayles.  Naïve T cells induce dendritic cells to secrete IL-12p40, not IL-12p70, during antigen presentation. Annual Meeting of the American Association of Immunologists, Boston MA, May 12-16, 2006.

Sayles, L.J. and K. Swier.  Leishmania major infection of CD43 knockout mice. Annual Biomedical Research Conference for Minority Students, Anaheim, CA, November 8-11, 2006.

Fatimah R. Macklin, Kevin Swier, Walid Al-Ghoul.  The Effect of thermal Injury on Mucosal Dendritic Cell Function. Annual Biomedical Research Conference for Minority Students, Hyatt Regency Atlanta, Atlanta, Georgia, Nov 2-5, 2005.

Leslie J. Sayles, Kevin Swier.  Effect of anti-CD40 on IL-12 Secretion in Bone Marrow Macrophages. Annual Biomedical Research Conference for Minority Students, Hyatt Regency Atlanta, Atlanta, Georgia, Nov 2-5, 2005.

Jermaine M. Stephens, Kevin Swier, Jeanette Bartley.  The Effect of Leishmania major on the Interaction Between Macrophages and Naïve T cells. Annual Biomedical Research Conference for Minority Students, Hyatt Regency Atlanta, Atlanta, Georgia, Nov 2-5, 2005.

Bartley, Jeanette, and K. Swier. 2003.  Induction of IL-12 from macrophages by naïve T cells during antigen presentation. Annual Biomedical Research Conference for Minority Students (ABRCMS), San Diego CA, Oct 15-19, 2003. 

Castro, Ramon, J. Craig, E. Peters, and K. Swier.  2003.  L. major amastigotes segregate into separate parasitophorous vacuoles during replication in vitro. Annual Biomedical Research Conference for Minority Students (ABRCMS), San Diego CA, Oct 15-19, 2003.

Douglas, T.S., R. Castro, K. Swier and W. Sherman.  2003. Leishmania major induces interleukin (IL)-12 in B10.D2 macrophages. Annual Biomedical Research Conference for Minority Students (ABRCMS), San Diego CA, Oct 15-19, 2003. 

Lewis, La Geisha R., and K. Swier.  2003.  Leishmania infected bone marrow macrophages can be induced to produce IL-12. Annual Biomedical Research Conference for Minority Students (ABRCMS), San Diego CA, Oct 15-19, 2003. 

Bartley, Jeanette, and K. Swier. 2003. Induction of IL-12 from macrophages by naïve T cells during antigen presentation. Poster, Annual Biomedical Research Conference for Minority Students, San Diego CA, Oct 15-19, 2003.

Castro, Ramon, J. Craig, E. Peters, and K. Swier. 2003. L. major amastigotes segregate into separate parasitophorous vacuoles during replication in vitro. Poster, Annual Biomedical Research Conference for Minority Students, San Diego CA, Oct 15-19, 2003.

Douglas, T.S., R. Castro, K. Swier and W. Sherman. 2003. Leishmania major induces interleukin (IL)-12 in B10.D2 macrophages. Poster, Annual Biomedical Research Conference for Minority Students, San Diego CA, Oct 15-19, 2003.

Lewis, La Geisha R., and K. Swier. 2003. Leishmania infected bone marrow macrophages can be induced to produce IL-12. Poster, Annual Biomedical Research Conference for Minority Students, San Diego CA, Oct 15-19, 2003.

Bussell, Avida N., Sherise Borum, Sundeep Grewal, and Kevin Swier. 2002. Leishmania major inhibits IL-12 transcription induced by naïve Leishmania antigen-specific T cells. FASEB J. 16 (5): A1068.

Castro, Ramon, Tiffany Jordan, Khara Scott, Joyce Craig, and Kevin Swier. 2002. L. major amastigotes segregate into separate parasitophorous vacuoles during replication in vitro and in vivo. FASEB J. 16(5): A1068.

Bussell, Avida, Sherise Borum, Sundeep Grewal and Kevin Swier, 2001. Leishmania major inhibits IL-12 transcription induced by naive Leishmania antigen-specific T cells. Poster, 30th Annual Autumn Immunology Conference, Chicago, IL November 17-19, 2001.

Castro, Ramon, Tiffany Jorndan, Khara Scott, Joyce Craig and Kevin Swier, 2001. L. major amastigotes segregate into separate parasitophorous vacuoles during replication in vitro and in vivo. Poster, 30th Annual Autumn Immunology Conference, Chicago, IL November 17-19, 2001.

Foster, Kelly, K. Scott, L. Reynolds, J. Craig and K. Swier. Comparing parasitophorous vacuoles (PVs) formed by Leishmania major infection of macrophages in vivo and in vitro. 11th Annual Student Research Conference, Chicago State University, March 31, 2000.

Bussell, Avida, and Kevin Swier. Naive CD4 T cells may induce IL-12 production of L. major-infected macrophages following antigen presentation. 11th Annual Student Research Conference, Chicago State University, March 31, 2000.

Borum, Sherise, K. Swier, A. Bussell, and T. Cotharn. The role of costimulatory molecules in the priming of naive T cells by Leishmania major-infected macrophages. 11th Annual Student Research Conference, Chicago State University, March 31, 2000.

Bussell, Avida, M. Luckett, S. Borum, and K. Swier. Leishmania major inhibits macrophage IL-12 transcription. Poster, National Minority Research Symposium, Washington, D.C., November 8-11, 2000.

Castro, Ramon, K. Foster, K. Scott, L. Reynolds, J. Craig, T. Cotharn, and K. Swier. Characterization of parasitophorous vacuoles in macrophages infected with Leishmania major. Poster, National Minority Research Symposium, Washington, D.C., November 8-11, 2000.

Bussell, Avida, M. Luckett, S. Borum, and K. Swier. Leishmania major inhibits macrophage IL-12 transcription induced by naive Leishmania antigen-specific T cells. Poster, 29th Annual Autumn Immunology Conference, Chicago, IL November 19-21, 2000.

Castro, Ramon, K. Foster, K. Scott, L. Reynolds, J. Craig, and K. Swier. Characterization of parasitophorous vacuoles formed by Leishmania major infection of macrophages. Poster, 29th Annual Autumn Immunology Conference, Chicago, IL November 19-21, 2000.

Wu, Shenhong, C. Beeson, K. Swier, and A.J. Sant. 2000. Antigen presentation regulated by DM can be predicted from the kinetic stability of peptide-MHC class II complexes. Poster, 29th Annual Autumn Immunology Conference, Chicago, IL November 19-21, 2000.

Khara Scott and Kevin Swier. Electron microscopic analysis of the parasitophorous vacuole in macrophages from the lymph node of Leishmania major-infected mice. Poster/Oral Presentation, Chicago Allicance for Minority Participation Undergraduate Research Conference, Illinois Institute of Technology, Chicago, IL April 9-10, 1999.

Scott, K., B. Evans, L. Reynolds, J. Craig, and K. Swier. The ultrastructure of the draining lymph node of Leishmania major-infected mice. Poster, 27th Annual Meeting of the Autumn Immunology Conference, Chicago, IL, Nov 20-22, 1998.