Date Available


Year of Publication


Degree Name

Doctor of Philosophy (PhD)

Document Type





Veterinary Science

First Advisor

Dr. Thomas M. Chambers


Dendritic cells (DC) are a heterogeneous population of hematopoietic cells that play a versatile role in orchestrating immune responses against an array of invading pathogens, including influenza virus. These cells reside in lymphoid organs as well as in non-lymphoid tissues such as mucosal surfaces of respiratory and gastro-intestinal system. Recent investigations have suggested that in the steady state, dendritic cells are derived mainly from bone marrow precursor cells without a monocytic intermediate whereas during inflammation or infection, monocytes readily differentiate to generate monocyte derived dendritic cells (MoDC). The ability of virus infected monocytes to differentiate into MoDC was investigated and the results demonstrated that in vitro infection of monocytes with influenza virus impaired their development into MoDC. It was also observed that influenza infection of monocytes, pre-treated with GM-CSF and IL-4 for DC differentiation, was minimally-productive and non-cytopathic. In spite of successful viral genome transcription, viral protein synthesis was restricted at an early stage. However, despite of the limited replication, influenza virus infected monocytes failed to develop the distinctive DC- like morphology when cultured with GM-CSF and IL- 4 as compared to their mock infected counterparts. Infected cells, after 4 days in culture, expressed reduced amounts of CD11c, CD172a (myeloid marker), CD1w2 (CD1b) and CCR5. Influenza virus infected monocytes also retained substantial non-specific esterase activity, a characteristic for monocytes and macrophages. Antigen presentation capability of infected cells was also affected as indicated by decreased endocytosis. Production of IL-12, a pro-inflammatory cytokine and IL-10, a reciprocal inhibitory cytokine, was coordinately modified in influenza virus infected monocytes in order to arrest their differentiation into DCs. At least limited viral replication was necessary to impede the differentiation process completely. However, viral NS1 protein activity, as evidenced with a mutant influenza virus, was not essential for this inhibition. This identified a new strategy by influenza virus to interfere with DC differentiation and evade a virus specific immune response.



To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.