Infectious Disease: Eric G. Pamer

Eric G. Pamer, MD Eric G. Pamer, MD Head, Division of General Medicine; Chief, Infectious Diseases Service; Enid A. Haupt Chair in Clinical Invesgation; Director, The Lucille Castori Center for Microbes, Inflammation and Cancer; Member, Immunology Program, Sloan Kettering Institute

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

Carles Ubeda, Ying Taur, Robert R. Jenq, Michele J Equinda, Tammy Son, Miriam Samstein, Agnes Viale, Nicholas D Socci, Marcel R van den Brink, Mini Kamboj, and Eric G Pamer. Intestinal domination by Vancomycin-resistant Enterococcus precedes bloodstream invasion in humans. Journal of Clinical Investigation. 2010 [In Press]

Kamboj M, Chung D, Seo S, Pamer E, Sepkowitz K, Jakubowski A, Papanicolaou G. The Changing Epidemiology of Vancomycin-resistant Enterococcus (VRE) Bacteremia in Allogeneic Hematopoietic Stem Cell Transplant (HSCT) Recipients. Biol Blood Marrow Transplant. 2010 May 25. [Epub ahead of print] [PubMed Abstract]

Shi C, Velazquez P, Hohl TM, Leiner I, Dustin ML, Pamer EG. Monocyte trafficking to hepatic sites of bacterial infection is chemokine-independent and directed by focal ICAM-1 expression. Journal of Immunology. 2010 Jun 1;184(11):6266-74. [PubMed Abstract]

Redelman-Sidi G, Sepkowitz KA, Huang CK, Park S, Stiles J, Eagan J, Perlin DS, Pamer EG, Kamboj MJ. 2009 H1N1 influenza infection in cancer patients and hematopoietic stem cell transplant recipients. J Infect. 2010 Apr;60(4):257-63. [PubMed Abstract]

Amigues I, Cohen N, Seo S, Chung D, Jakubowski A, Barker J, Pamer E, Papanicolaou G. Hepatic safety of voriconazole after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2010 Jan;16(1):46-52. [PubMed Abstract]

Serbina NV, Hohl TM, Cherny M, Pamer EG. Selective expansion of the monocytic lineage directed by bacterial infection. J Immunol. 2009 Aug 1;183(3):1900-10. [PubMed Abstract]

Mircescu M, Lipuma L, van Rooijen N, Pamer, EG, and Hohl TM. Essential role for neutrophils but not alveolar macrophages at early time points following Aspergillus fumigatus infection. J Infect Dis. 2009 Aug 15;200(4):647-56. [PubMed Abstract]

Serbina NV, Cherny M, Shi C, Bleau SA, Collins NH, Young JW, Pamer EG. Distinct responses of human monocyte subsets to Aspergillus fumigatus conidia. J Immunol. 2009 Aug 15;183(4):2678-87. [PubMed Abstract]

Jia T, Pamer EG. Immunology. Dispensable but not irrelevant. Science. 2009 Jul 31;325(5940):549-50. No abstract available.

Jia T, Leiner I, Dorothee G, Brandl K, Pamer EG. MyD88 and Type I interferon receptor-mediated chemokine induction and monocyte recruitment during Listeria monocytogenes infection. J Immunol. 2009 Jul 15;183(2):1271-8. [PubMed Abstract]

Rivera A, Collins N, Stephan MT, Lipuma L, Leiner I, Pamer EG. Aberrant tissue localization of fungus-specific CD4+ T cells in IL-10-deficient mice. J Immunol. 2009 Jul 1;183(1):631-41. [PubMed Abstract]

Pamer EG. Tipping the balance in favor of protective immunity during influenza virus infection.Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):4961-2. Review. No abstract available.

Mihu CN, Schaub J, Kesh S, Jakubowsi A, Sepkowitz K, Pamer EG, Papanicolaou GA. Risk factors for late Staphylococcus aureus bacteremia after allogeneic hematopoietic stem cell transplantation: a single-institution, nested case-controlled study. Biol Blood Marrow Transplant. 2008 Dec; 14(12):1429-33. [PubMed Abstract]

Kamboj M, Gerbin M, Huang CK, Brennan C, Stiles J, Balashov S, Park S, Kiehn TE, Perlin DS, Pamer EG, Sepkowitz KA. Clinical characterization of human metapneumovirus infection among pateints with cancer. J Infect. 2008 Dec;57(6):464-71. [PubMed Abstract]

Serbina NV, Pamer EG. Coordinating innate immune cells to optimize microbial killing. Immunity. 2008 Nov;29(5):672-4. [PubMed Abstract]

Pamer EG. TLR polymorphisms and the risk of invasive fungal infections. New England Journal of Medicine. 2008 Oct 23;359(17):1766-77. [PubMed Abstract]

Gallegos AM, Pamer EG, Glickman MS. Delayed Protection by ESAT-6-Specific Effector CD4 (+) T Cells after Airborne M. Tuberculosis Infection. Journal of Experimental Medicine. 2008; 205(10):2359-68. [PubMed Abstract]

Brandl K, Plitas G, Mihu CN, Ubeda C, Jia T, Fleisher M, Schnabl B, DeMatteo RP, Pamer EG. Vancomycin-resistant enterococci exploit innate immune deficits induced by antibiotic treatment. Nature. 2008; 455(7214):804-7. [PubMed Abstract]

Hohl TM, Feldmesser M, Perlin DS, Pamer EG. Caspofungin Modulates Inflammatory Responses to Aspergillus fumigatus through State-Specific Effects on Fungal beta-Glucan Exposure. Journal of Infectious Diseases. 2008; 198(2):176-85. [PubMed Abstract]

Jia T, Serbina N, Brandl K, Zhong MX, Leiner IM, Charo IF, Pamer EG. Additive roles for MCP-1 and MCP-3 in CCR2-mediated recruitment of inflammatory monocytes during Listeria monocytogenes infection. Journal of Immunology. 2008; 180(10): 6846-53. [PubMed Abstract]

Pamer EG. Immune responses to commensal and environmental microbes. Nature Immunology. 2007; 8(11): 1173-8. [PubMed Abstract]

Brandl K, Plitas G, Schnabl B, Dematteo RP, and Pamer EG. MyD88-mediated signals induce the bactericidal lectin RegIII {gamma} and protect mice against intestinal Listeria monocytogenes infection. Journal of Experimental Medicine. 2007; 204(8):1891-900. [PubMed Abstract]

Biswas PS, Pedicord V, Ploss A, Menet E, Leiner I, Pamer EG. Pathogen-specific CD8 T cell responses are directly inhibited by IL-10. Journal of Immunology. 2007; 179(7): 4520-8. [PubMed Abstract]

Mihu CN, King E, Yossepovitch O, Taur Y, Jakubowski A, Pamer E, Papanicolaou, GA. Risk factors and attributable mortality of late aspergillosis after T-cell depleted hematopoietic stem cell transplantation. Transpl Infect Dis. 2007; 10(3):162-7. [PubMed Abstract]

Brandl K, Plitas G, Schnobl B, DeMatteo RP, Pamer, EG. My D88-mediated signals induce the bactericidal lectin RegIII gamma and protect mice against intestinal Listeria monocytogenes infection. Journal of Experimental Medicine. 2007; 204(8):1891-900. [PubMed Abstract]

Almyroudis NG, Jakubowski A, Jaffe D, Sepkowitz K, Pamer E, O'Reilly RJ, Papanicolaou GA. Predictors for persistent cytomegalovirus reactivation after T-cell-depleted allogeneic hematopoietic stem cell transplantation. Transpl Infect Dis. 2007; 9(4):286-94. [PubMed Abstract]

Symeonidis N, Jakubowski A, Pierre-Louis S, Jaffe D, Pamer EG, Sepkowitz K, O'Reilly RJ, Papanicolaou GA. Invasive adenoviral infections in T-cell-depleted allogeneic hematopoietic stem cell transplantation: high mortality in the era of cidofovir. Transpl Infect Dis. 2007; 9(2): 108-13. [PubMed Abstract]

Tuma R, Almyroudis N, Sohn S, Panageas K, Rice R, Galinkin D, Blain M, Montefusco M, Pamer E, Nimer S, and Kewalramani T. The serum IL-12:IL-6 ratio reliably distinguishes infectious from non-infectious causes of fever during autologous stem cell transplantation. Cytotherapy. 2006; 8(4):327-34. [PubMed Abstract]

Zakrzewski JL, Kochman AA, Lu SX, Terwey TH, Kim TD, Hubbard VM, Muriglan SJ, Suh D, Smith OM, Grubin J, Patel N, Chow A, Cabrera-Perez J, Radhakrishnan R, Diab A, Perales MA, Rizzuto G, Menet E, Pamer EG, Heller G, Zuniga-Pflucker JC, Alpdogan O, and van den Brink MR. Adoptive transfer of T-cell precursors enhances T-cell reconstitution after allogeneic hematopoietic stem cell transplantation. Nature Medicine. 2006; 12(9):1039-47. [PubMed Abstract]

Hohl TM, and Pamer EG. Cracking the fungal armor. Nature Medicine. 2006; 12(7):730-2. [PubMed Abstract]

Kappel BJ, Pinilla-Ibarz J, Kochman AA, Eng JM, Hubbard VM, Leiner I, Pamer EG, Heller G, van den Brink MR, and Scheinberg DA. Remodeling specific immunity by use of MHC tetramers: demonstration in a graft-versus-host disease model. Blood. 2006; 107(5): 2045-51. [PubMed Abstract]

Kesh S, Mensah NY, Peterlongo P, Jaffe D, Hsu K, van den Brink MR, O'Reilly R, Pamer EG, Satagopan J, and Papanicolaou GA. TLR1 and TLR6 polymorphisms are associated with susceptibility to invasive aspergillosis after allogeneic stem cell transplantation. Annals of the New York Academy of Science. 2006; 1062:95-103. [PubMed Abstract]

Serbina NV, and Pamer EG. Monocyte emigration from bone marrow during bacterial infection requires CCR2-mediated signals. Nature Immunology. 2006; 7(3): 311-7. [PubMed Abstract]

Rivera A, Ro G, Van Epps HL, Simpson T, Leiner I, Sant'Angelo D. B., and Pamer EG. Innate immune activation and CD4+ T cell priming during respiratory fungal infection. Immunity. 2006; 25(4):665-75. [PubMed Abstract]