Immunology & Infectious Diseases

Simon Newman

Simon Newman, PhD

Int Med-Infect Disease

Professor

  • MSB 7264
  • P. O. Box 670560
  • Cincinnati OH 45267
  • (513)558-4704
  • newmansl@uc.edu

Research Summary

Research in my laboratory focuses on understanding the biology and biochemistry of the interaction between monocyte/macrophages, neutrophils, and dendritic cells and pathogenic fungi, in particular Histoplasma capsulatum.

We have demonstrated that Histoplasma yeasts have a dual strategy for surviving in human macrophages. First, intraphagosomal pH is maintained at about 6.5 to minimize the activity of lysosomal acid hydrolases and to allow the yeasts to obtain iron from transferrin. Second, Histoplasma yeasts inhibit phagolysosomal fusion. We also have shown that adherence of macrophages to type I collagen matrices rapidly activates macrophages to inhibit the replication of H. capsulatum yeasts by overcoming its capacity to inhibit phagolysosomal fusion. Current projects are directed to: 1) identify the combination of cytokines and extracellular matrix proteins that maximally activate macrophage anti-Histoplasma activity; and 2) to determine the mechanism(s) of macrophage-mediated fungicidal activity.

Most recently we have demonstrated that human dendritic cells phagocytose Histoplasma yeasts in the absence of serum, inhibit their intracelluar replication, and even kill and degrade many of the yeasts. Current projects are directed towards: 1) characterizing the initial interaction between human and murine dendritic cells and H. capsulatum yeasts and conidia; 2) characterizing the interaction between Histoplasma-infected dendritic cells and T cells, with particular emphagsis on the requirement for dendritic cell CD80/CD86 and CD40 interaction with T-cell CD28 and CD40L, respectively, in promoting T cell proliferation and cytokine production; and 3) determining the role of dendritic cells in vivo in a murine model of pulmonary histoplasmosis.

Dr. Newman is a well-established investigator in macrophage function and has recently gained recognition for his expertise in studies of host defenses against fungi. His specific research interests involve analysis of the interaction of H. capsulatum yeasts and conidia with human monocytes, macrophages, neutrophils and dendritic cells. He is a past Associate Editor of The Journal of Immunology and an Editorial Board member of Infection and Immunity. He also is an ad hoc reviewer for The Journal of Experimental Medicine, The Journal of Clinical Investigation, Proceedings of the National Academy of Sciences, USA, The Journal of Infectious Diseases, Medical Mycology, The American Journal of Pathology, American Review of Respiratory Disease, Arthritis and Rheumatism, The American Journal of Medical Sciences, Journal of Laboratory and Clinical Medicine, Kidney International, Natural Immunity and Blood. His published works include approximately 50 articles and approximately 60 abstracts.

Recent Publications

Gomez FJ, Pilcher-Roberts R, Alborzi A, Newman SL. Histoplasma capsulatumcyclophilin A mediates attachment to dendritic cell VLA-5. J Immunol. 2008 Nov15;181(10):7106-14. PubMed PMID: 18981131.

Hilty J, Smulian AG, Newman SL. The Histoplasma capsulatum vacuolar ATPase is required for iron homeostasis, intracellular replication in macrophages andvirulence in a murine model of histoplasmosis. Mol Microbiol. 2008Oct;70(1):127-39. Epub 2008 Aug 11. PubMed PMID: 18699866; PubMed Central PMCID: PMC2570752. 

Newman SL, Gootee L, Hilty J, Morris RE. Human macrophages do not requirephagosome acidification to mediate fungistatic/fungicidal activity againstHistoplasma capsulatum. J Immunol. 2006 Feb 1;176(3):1806-13. PubMed PMID:16424211.

Gildea LA, GM Ciraolo, RE Morris, and SL Newman. 2005. Human dendritic cell antifungal activity against Histoplasma capsulatum is mediated by phagolysosomal fusion. Infect. Immun. 73:6803-6811.

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