Human Adenoid Organ Culture: A Model to Study the Interaction of Influenza A with Human Nasopharyngeal Mucosa

Abstract

Previous studies of infections with influenza A in animal models have stressed the tropism of this virus for the upper respiratory tract. To assess the interaction of influenza A virus with human respiratory tissue, we maintained adenoids, consisting of ciliated epithelium with underlying lymphoid follicles, in organ culture. When the organ cultures were inoculated with wild-type influenza A/Alaska (H3N2), epithelial damage and migration of inflammatory cells from the follicles into the lamina propria were seen. Growth of the virus and ciliary damage in infected organ cultures from seronegative donors were significantly greater than that seen in organ cultures from seropositive donors. Adenoidal lymphocytes were then studied to determine which factors might modulate infectivity. Specific in vitro production of antibody to influenza A/Alaska was demonstrated by adenoidal lymphocytes from seropositive donors, whereas lymphocytes from seronegative donors did not produce antibody. The human adenoid organ culture provides an attractive model to study the pathogenesis of influenza A infections and the resultant local immune response.

Parenteral Influenza Vaccination Influences Mucosal and Systemic T Cell–Mediated Immunity in Healthy Adults

“…Studies of unvaccinated adults have demonstrated influenza-specific antibody-forming cells (AFCs) in nasal, PT, and adenoidal mucosal tissue [8,9], which suggests that natural infection also elicits a humoral response in the mucosal compartment. Clearly, in any attempt to enhance immunity to influenza through vaccination, it would be advantageous to enhance local and systemic immunity.…”

Growth of influenza A virus in primary, differentiated epithelial cells derived from adenoids

“…Respiratory epithelium has not been readily accessible for in vivo study beyond quantitation of virus in secretions or for in vitro study in tissue or organ culture. Under standard tissue culture conditions, epithelial cells are overgrown by fibroblasts and sustained viability of adenoid human organ culture has been difficult to achieve (5). Human fetal tissue was used in early experiments to examine virus replication in tracheal organ rings; however, this tissue is no longer available (11).…”

The role of M cells of human nasopharyngeal lymphoid tissue in influenza virus sampling

“…It was found that influenza virus infection caused the loss of ciliated and basal epithelial cells in an adenoid organ culture and that inflammatory cells from the lymphoid follicles migrated into the lamina propria [3]. It is thought that human influenza virus binds to ciliated cells, but not to non-ciliated cells, of the tracheal epithelium and that functional receptors are expressed on the surfaces of only ciliated cells [2].…”