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Eric G. Pamer, MD Chief, Infectious Diseases Service
Member, Immunology Program
Sloan Kettering Institute |
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Phone
646-888-2679
Education
MD, Case Western Reserve University School of Medicine
Residencies
Internal Medicine, UCSD Medical Center
Fellowship
Infectious Diseases, UCSD Medical Center
Board Certification
Internal Medicine; Infectious Diseases
Academic Appointments
Weill Medical College of Cornell University
Hospital Appointments
Memorial Hospital
Research Interests
Our laboratory is investigating innate and adaptive immune responses to infection by pathogenic organisms. We have established two model systems to characterize innate immunity and antigen specific T cell responses. The first focuses on the intracellular bacterium Listeria monocytogenes. Mice infected with L. monocytogenes develop a rapid inflammatory response that is followed by a robust and highly protective T cell mediated immune response. The early inflammatory response is essential for survival and monocyte recruitment to sites of infection is central to this process. Our laboratory is characterizing the recruitment of monocytes from the bone marrow into the bloodstream and infected tissues following systemic infection with L. monocytogenes. We have found that the CCR2 chemokine receptor is essential for monocyte emigration from the bone marrow and that cellular infection with L. monocytogenes induces the production of MCP-1, the ligand for CCR2. Current studies are investigating the in vivo signaling mechanisms that drive the recruitment of inflammatory cells from bone marrow to infected tissues.
To characterize adaptive immunity, we have determined the antigen specificity of CD8 T cells responding to L. monocytogenes and, using MHC class I tetramers, have measured and characterized the in vivo expansion of distinct T cell populations during the course of active bacterial infection. These studies have shown that CD8 T cells responding to L. monocytogenes infection can be divided into two distinct populations that differ in their MHC restriction, peptide specificity and in vivo response kinetics. The first T cell population to respond to L. monocytogenes infection is restricted by H2-M3 MHC class Ib molecules, which present N-formyl methionine bacterial peptides to CD8 T cells. This T cell response is very rapid and quantitatively substantial, but it does not give rise to a large memory T cell population. The second T cell population is restricted by conventional MHC class Ia molecules. This T cell response is slower than the H2-M3 restricted T cell response but it provides a large populations of memory T cells which protect mice from secondary infection with L. monocytogenes. Our laboratory is currently investigating the cellular and molecular mechanisms that are responsible for the rapid primary response of H2-M3 restricted T cells and the dramatic memory response of MHC class Ia restricted T cells. We believe that these studies will provide fundamental information about T cell responses to bacterial infection and the generation and maintenance of T cell memory.
Our second area of interest concerns the immune response to the fungal pathogen Aspergillus fumigatus. This spore forming mold is an important cause of infection in the immunocompromised host. Our laboratory is characterizing the recruitment of neutrophils and monocytes to the lungs of mice infected with A. fumigatus spores. We have found that Dectin-1, a receptor expressed on alveolar macrophages, plays an important role in the innate immune response to fungal spores. Our studies demonstrate that germinating A. fumigatus spores trigger innate immune responses. Selective responses to germinating spores result from stage-specific display on beta-glucans, a major ligand for Dectin-1, on the spore surface.
We are also characterizing the CD4 T cell response to A. fumigatus infection. Studies in bone marrow transplant models have demonstrated that CD4 T cells can provide protection against invasive A. fumigatus infections. We have generated T cell receptor transgenic mice that are specific for A. fumigatus and are using these mice to characterize in vivo priming, expansion and differentiation of fungus specific CD4 T cells. Current studies are determining the impact of innate immune responses on the subsequent differentiation of A. fumigatus specific CD4 T cells.
Recent Publications
Lauvau, G., Vijh, S., Kong, P., Horng, T., Kerksiek, K., Serbina, N., Tuma, R., and E.G. Pamer (2001) Priming of memory but not effector CD8 T cells by a killed bacterial vaccine. Science. 294:1735-1739. [PubMedAbstract]
Serbina, N., Salazar-Mather, T., Biron, C., Kuziel, W., and Pamer, E. (2003) TNF/iNOS-producing dendritic cells Mediate innate immune defense against bacterial infection. Immunity. 19(1):59-70. [PubMedAbstract]
Serbina, N., Kuziel, W., Flavell, R., Akira, S., Rollins, B., and Pamer, E. (2003) Sequential MyD88-independent and dependent activation of innate immune responses to intracellular bacterial infection. Immunity. 19(6):891-901. [PubMedAbstract]
Wong, P. and E.G. Pamer (2003) Feedback regulation of pathogen specific T cell priming. Immunity. 18(4): 499-511. [PubMedAbstract]
Serbina, N., and E.G. Pamer. (2003) Giving credit where credit is due. Science. 301: 1856-7. [PubMedAbstract]
Pamer, E.G. (2004) Immune responses to Listeria monocytogenes. Nature Reviews Immunology. 4(10): 812-821. [PubMedAbstract]
Ploss, A., Tran, A., Menet E., Leiner, I., and E.G. Pamer. (2005) Cross-recognition of N-formylmethionine peptides is a general characteristic of H2-M3 restricted CD8+ T cells. Infection and Immunity. 73: 4423-4426. [PubMedAbstract]
Ploss, A., Leiner, I., and E.G. Pamer. (2005) Distinct regulation of H2-M3-restricted memory T cell responses in lymph node and spleen. Journal of Immunology. 175(9): 5998-6005. [PubMedAbstract]
Rivera, A., Van Epps, H., Rizzuto, G., and E.G. Pamer. (2005) Distinct CD4+/- T cell responses to live and heat-inactivated Aspergillus fumigatus conidia. Infection and Immunity. 73(11): 7170-7179. [PubMedAbstract]
Hohl, T.M., Van Epps, H., Rivera, A., Morgan, L., Chen, P., Feldmesser, M., and E.G. Pamer. (2005) Aspergillus fumigatus Triggers Inflammatory Responses by Stage-Specific beta-Glucan Display. PLoS Pathogens. 1(3): 232-240. [PubMed Abstract] )
Kesh, S., Mensah, N.Y., Peterlongo, P., Jaffe, D., Hsu, K., vanden Brink, M., O'Reilly, R., Pamer, E., Satagopan, J., andPapanicolaou, G.A. TLR1 and TLR6 polymorphisms are associated withsusceptibility to invasive aspergillosis after allogeneic stem celltransplantation. Ann N Y Acad Sci. 2006; 1062:95-103. [PubMed Abstract]
Serbina, N.V., and Pamer, E.G. (2006). Monocyte emigration from bone marrow during bacterial infection requires CCR2-mediated signals. Nat. Immunol. Mar 7(3):311-7. [PubMed Abstract]
Rivera, A., Ro, G., Van Epps, H.L., Simpson, T., Leiner, I., Sant' Angelo, D.B., and Pamer, E.G. (2006). Innate immune activation and CD4+ T cell priming during respiratory fungal infection. Immunity. 25(4):665-75. [PubMed Abstract]
Hohl, T.M., and Pamer, E.G. (2006). Cracking the fungal armor. Nature Medicine. 12(7):730-2. [PubMed Abstract]
Hohl, T.M., Rivera, A., and Pamer, E.G., (2006). Immunity to fungi. Current Opinion in Immunology. 18(4):465-72. [PubMed Abstract]
Biswas, P.S., Pedicord, V., Ploss, A., Menet, E., Leiner, I., and Pamer, E.G.(2007). Pathogen-specific CD8 Tcell responses are directly inhibited by IL-10. The Journal of Immunology. [PubMed Abstr]
Brandl, K., Plitas, G., Schnabl, B., Dematteo, R.P., and Pamer, E.G. (2007). MyD88-mediated signals induce the bactericidal lectin RegIII{gamma} and protect mice against intestinal Listeria monocytogenes infection. Journal of Experimental Medicine. 204(8):1891-900.[PubMed Abstract]
