CURRENT RESEARCH INTERESTS:
Innate Immunity and Bacterial Enteric Infection
My major interest is the study of the host-pathogen relationship that exists between us and bacteria. My current work focuses on Campylobacter jejuni, a Gram-negative, invasive organism that is a leading cause of food-borne bacterial enteritis in the United States. In immunocompromised persons and in developing countries, Campylobacter causes severe disease that may disseminate, leading to death. Despite the large burden of disease caused by Campylobacter, less is known about the pathogenesis of C. jejuni than of Enterobacteriaceae such as Salmonella. However, the usually self-limited nature of C. jejuni infection suggests that innate immune mechanisms may be important in controlling the disease.
Among the many mammalian innate host defenses are toxic reactive nitrogen species derived from nitric oxide, produced by the activity of inducible nitric oxide synthase (iNOS, also known as NOS2). This enzyme is present in professional phagocytes as well as epithelial cells, and contributes to host defense against other microbes such as Mycobacteria and Listeria. We propose that C. jejuni also is susceptible to the antimicrobial effects of reactive nitrogen species and may employ specific mechanisms to resist nitrosative stress. In support of our hypothesis, our data with murine bone marrow-derived macrophages show that production of nitric oxide and related reactive nitrogen species contribute to the killing of C. jejuni. In a related project, we are investigating the mechanisms and genes that C. jejuni employs in response to host-derived nitrosative stress using site-directed and transposon-mutagenesis approaches. Finally, we are using confocal microscopy to examine the intracellular trafficking of C. jejuni in phagocytic and non-phagocytic cells to determine how bacterial survival may be affected when normal pathways are perturbed by bacterial virulence strategies. |
Selected Publications |
| 1. |
Iovine N, Pursnani, S, Voldman, A, Wasserman, A, Blaser, MJ and Weinrauch, Y. Reactive nitrogen species contribute to innate host defense against Campylobacter jejuni. Infect Immun 2007; in press. |
| 2. |
Iovine NM. Innate Immunity in Campylobacter Infections. In: Campylobacter. Nachamkin I and Blaser MJ, Ed. 3rd ed. Washington DC: ASM Press; in press. |
| 3. |
Kang JM, Iovine NM, Blaser MJ. A paradigm for direct stress-induced mutation in prokaryotes. Faseb J 2006;20(14):2476-85. |
| 4. |
Iovine, N. and Blaser, MJ. Antibiotics in animal feed and spread of resistant Campylobacter from poultry to humans. Emerg. Infect. Dis. 2004; 10:1158–9. |
| 5. |
Iovine, N.M., Eastvold, J., Elsbach, P., Weiss, J.P., and Gioannini, T.L. The carboxyl-terminal domain of closely related endotoxin-binding proteins determines the target of protein-lipopolysaccharide complexes. J. Biol. Chem. 2002. 277:7970-7978. |
| 6. |
Tobias PS, Soldau K, Iovine NM, Elsbach P, Weiss J. Lipopolysaccharide (LPS)-binding proteins BPI and LBP form different types of complexes with LPS. J Biol Chem 1997;272(30):18682-5. |
| 7. |
Iovine NM, Elsbach P, Weiss J. An opsonic function of the neutrophil bactericidal/permeability-increasing protein depends on both its N- and C-terminal domains. Proc Natl Acad Sci U S A 1997;94(20):10973-8. |
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