Induction of polymorphonuclear leukocyte response by human cytomegalovirus.
Neutrophils are important in the defense against bacterial infections, by ingesting and killing invading microorganisms. Because of the higher incidence of bacterial infections in patients with active human cytomegalovirus (HCMV) infections, we hypothesized that HCMV-infected neutrophils were inefficient in eliminating the bacteria. Therefore, we mock infected or infected neutrophils with HCMV by contact with HCMV-infected human pulmonary artery endothelial cells. We found that HCMV infection without N-formyl-methionyl-leucyl-phenylalanine (fMLP) stimulation increased the surface expression of CD11b to the same extent as fMLP stimulation of mock infected cells. Also, HCMV-infected neutrophils became more efficient in phagocytosing serum opsonized yeast particles than mock infected cells. Furthermore, we observed an increase in intracellular free calcium and chemiluminescence in HCMV-infected cells, in response to fMLP compared to fMLP-treated mock cells. We also found that apoptosis was significantly inhibited in HCMV-infected neutrophils. In conclusion, our results suggest that neutrophils become more effective in performing their effector functions when infected with HCMV. Thus, the higher incidence of bacterial infections in HCMV patients might not be due directly to a dysfunction in the neutrophils. Instead, the fact that apoptosis is inhibited may cause over-reactive neutrophils to remain in the tissues, where they will start leaking their contents, damaging the tissues and contributing to inflammatory processes.
Skarman
Petra Jerström
PJ
Department of Medicine, Center for Molecular Medicine, L8:03, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
Rahbar
Afsar
A
Xie
Xun
X
Söderberg-Nauclér
Cecilia
C
D017209:Apoptosis / Q000276:immunology; D039481:CD11b Antigen / Q000096:biosynthesis / Q000276:immunology; D018821:CD18 Antigens / Q000096:biosynthesis; D002118:Calcium / Q000378:metabolism; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D042783:Endothelial Cells; D005347:Fibroblasts / Q000821:virology; D005434:Flow Cytometry; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D010084:Oxidation-Reduction; D010587:Phagocytosis / Q000276:immunology; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000276:immunology; D014158:Transcription, Genetic
D039481:CD11b Antigen; D018821:CD18 Antigens; D012367:RNA, Viral; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002118:Calcium