Bactericidal activity of a monocytic cell line (THP-1) against common respiratory tract bacterial pathogens is depressed after infection with respiratory syncytial virus.
Non-typable Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis and respiratory syncytial virus (RSV) are commonly isolated from patients during the course of chronic obstructive pulmonary disease (COPD). Earlier studies found that virus infection enhanced binding of bacterial respiratory pathogens to epithelial cells in vitro. The objective of the present study was to assess the effect of RSV infection of a human monocytic cell line on bactericidal activity and cytokine production in response to these bacterial respiratory pathogens. The effect of RSV infection on binding, uptake and intracellular killing of bacteria by a human monocytic leukaemia cell line, THP-1, was assessed. Cell culture supernates were examined with a mouse fibroblast cell assay for tumour necrosis factor-alpha (TNF-alpha) bioactivity. Expression of CD14, CD11a, CD18, CD15 and CD29 on uninfected and RSV-infected THP-1 cells was assessed by flow cytometry in relation to differences in bacterial binding. RSV infection of THP-1 cells significantly decreased their ability to bind and kill bacteria. Compared with uninfected cells, fewer bacteria bound to RSV-infected THP-1 cells and the surface antigens that have been reported to bind bacteria were expressed at lower levels on RSV-infected cells. RSV-infected cells incubated with bacteria exhibited less TNF-alpha bioactivity than uninfected cell incubated with bacteria. The results elucidate some of the mechanisms involved in the increased susceptibility of virus-infected patients to secondary bacterial infection. Reduced bacterial killing by virus-infected monocytes might contribute to reduced clearance of bacteria from the respiratory tract and damage elicited by the bacteria or cytokine response in COPD patients.
Raza
M W
MW
Blackwell
C C
CC
Elton
R A
RA
Department of Medical Microbiology and *Medical Statistics Unit, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG.
Weir
D M
DM
D000911:Antibodies, Monoclonal / Q000276:immunology; D002460:Cell Line; D006193:Haemophilus influenzae / Q000276:immunology*; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000382:microbiology* / Q000821:virology; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology; D001936:Moraxella catarrhalis / Q000276:immunology*; D018113:Respiratory Syncytial Virus, Human / Q000502:physiology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha