Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 2/3/2010
Publication Date: 7/1/2010
Citation: Fach, S.J., Olivier, A., Gallup, J.M., Waters, T.E., Ackermann, M., Lehmkuhl, H.D., Sacco, R.E. 2010. Differential Expression of Cytokine Transcripts in Neonatal and Adult Ovine Alveolar Macrophages in Response to Respiratory Syncytial Virus or Toll-Like Receptor Ligation. Veterinary Immunology and Immunopathology. 136(1-2):55-64. Interpretive Summary: We examined changes in lung white blood cells in response to infection of lambs with a respiratory virus. Further, we compared the response of lamb cells to the response of adult sheep. Our results indicate that the response of lamb cells to the respiratory virus differ from those of cells from adult animals. The impact of this research is that it is likely that the response of the neonatal cells may leave the young animal more susceptible to other infections.
Technical Abstract: Respiratory syncytial virus (RSV) infections are common in children less than 2 years of age and can be particularly severe in neonates and premature infants. Alveolar macrophages (AMphis) secrete cytokines or chemokines that participate in induction of the innate response to RSV and which may contribute to disease severity. Previously, we utilized a neonatal lamb model of RSV infection which mimics disease seen in neonatal infants. In the present studies, AMphi responses were compared after in vivo bovine RSV (BRSV) 375 or human RSV A2 infection of neonatal lambs. Both human and bovine strains of the virus induced a mixture of proinflammatory (IL-1beta, IL-6, IL-12p40) and immunoregulatory (IL-4, IL-10) mediators. In addition, BRSV induction of neonatal AMphi cytokine responses in vivo was compared to responses induced by in vitro infection. Neonatal AMphis transcribed less IL-4, IL-6, IL-12p40, and TNFalpha' but more IL-8 mRNA, after in vitro BRSV exposure when compared to gene expression observed in vivo. Neonatal and adult AMphis were permissive to in vitro BRSV infection and the virus was demonstrated to actively replicate within these cells. AMphis infected with BRSV were found to induce qualitatively different cytokine and chemokine gene transcription compared to responses elicited by TLR3 and TLR4 agonists. Levels of cytokine and chemokine expression in neonatal and adult AMphis do differ when stimulated with TLR agonists. In addition, these data suggest that neonatal AMphis are a source of type 2 cytokines during RSV infection which may contribute to the development of childhood asthma or allergies.