Date Approved

2005

Degree Type

Open Access Thesis

Degree Name

Master of Science (MS)

Department or School

Biology

Committee Member

Daniel L. Clemans, PhD, Chair

Committee Member

James L. VandenBosch, PhD, Member

Committee Member

Michael G. Angell, PhD, Member

Abstract

Nontypeable H. influenzae (NTHi) causes repeated respiratory infections characterized by a brisk inflammatory response that results in the expression and secretion of proinflammatory cytokines. We hypothesized that secreted and cell asssociated NTHi proteins mediate cellular interactions with respiratory epithelial cells, leading to the production of interleukin (IL)-8. We exposed human tracheal epithelial cells to H. influenzae strain Rd and compared the resulting profiles of IL-8 secretion. Putative H. influenzae Rd modulins were enriched from culture supernatant fluid. Proteome analysis of the enriched fractions revealed 27 candidate proteins. Further analysis of four proteins, ClpB, OmpP2, TonB, and RelA, suggested a potential role in the IL-8 response. A fifth protein, FtsH, showed no such response. Study of the other 22 proteins is required to understand their role in cytokine induction. These results suggest that factors other than lipooligosaccharide (LOS) contribute to IL-8 secretion.

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