INNATE IMMUNITY OF RESPIRATORY EPITHELIA: EFFECTS OF PRETERM BIRTH AND RESPIRATORY SYNCYTIAL VIRUS INFECTION

Authors: ACKERMANN, MARK - IOWA STATE UNIVERSITY; MEYERHOLZ, DAVID - IOWA STATE UNIVERSITY; GRUBOR, BRANKA - IOWA STATE UNIVERSITY; Lehmkuhl, Howard; Sacco, Randy; GALLUP, JACK - IOWA STATE UNIVERSITY; DERSCHEID, RACHEL - IOWA STATE UNIVERSITY; LAZIC, TANJA - IOWA STATE UNIVERSITY; FACH, SASHA - IOWA STATE UNIVERSITY; KAWASHIMA, KENJI - IOWA STATE UNIVERSITY

Submitted to: Conference Research Workers Disease Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 11/14/2004
Publication Date: 11/14/2004
Citation: Ackermann, M.R., Meyerholz, D.K., Grubor, B., Lehmkuhl, H.D., Sacco, R.E., Gallup, J.M., Derscheid, R., Lazic, T., Fach, S., Kawashima, K. 2004. Innate immunity of respiratory epithelia: effects of preterm birth and respiratory syncytial virus infection [abstract]. Conference of Research Workers in Animal Diseases. p. 136.

Interpretive Summary:

Technical Abstract: Preterm infants infected with respiratory syncytial virus (RSV) more often have severe infections than full term infants that require intensive care unit admission, supplemental oxygen, and mechanical ventilation. Adaptive immune responses and maternal antibody do not consistently afford protection and innate defenses against pre-term RSV infection have not been fully characterized. In addition to mucociliary clearance, respiratory epithelial cells protect against infection through the release of wide variety of well characterized substances such as lysozyme and also less understood antimicrobial factors such as antimicrobial peptides, anionic peptides, and surfactant proteins, all of which have become increasingly appreciated for their antimicrobial properties. In a lamb model of preterm and neonatal RSV infection, we have found that preterm lambs have more severe RSV infections than full term lambs, similar to disease in human infants. We have also determined that increased expression of innate immune factors released by epithelia in vivo, including sheep beta-defensin-1 (SBD-1) and surfactant protein A and D (SP-AD) are associated with viral clearance. RSV-infected lung epithelial cells retrieved by laser capture microdissection appears to have increased expression of innate immune factors and nearby, non-infected cells have even higher levels of expression, suggesting that infected respiratory epithelia and epithelia surrounding RSV-infected cells may produce innate immune factors in order for viral clearance and self-protection. We are currently assessing expression of innate immune factors by respiratory epithelia in response to growth factors and varying conditions in order to identify therapies that may enhance innate immunity in order to prevent RSV infection or enhance RSV clearance in neonates.