Cytomegalovirus induction of tumor necrosis factor-alpha by human monocytes and mucosal macrophages.
Cytomegalovirus (CMV) is a major cause of inflammatory organ disease in immunosuppressed persons. To elucidate the mechanisms of CMV-induced inflammation, we investigated whether tumor necrosis factor-alpha (TNF-alpha) was involved in the pathogenesis of CMV colitis in patients with AIDS. In in situ hybridization experiments, TNF-alpha mRNA was shown to be abundantly present in colonic mucosa from AIDS patients with CMV colitis but not in colonic mucosa from control (AIDS and normal) subjects. The TNF-alpha transcripts, identified in macrophage-like cells containing cytomegalic inclusions, were positively associated with CMV, but not HIV-1, within the mucosa. In in vitro experiments, a patient-derived isolate of CMV, but not HIV-1Ba-L, induced human monocytes to express TNF-alpha mRNA and to release increased levels of TNF-alpha peptide following stimulation. CMV induction of TNF-alpha may play a critical role in CMV-induced inflammation and, since TNF-alpha upregulates expression of HIV-1, offers a mechanism by which CMV could serve as a co-factor for HIV-1 expression without both viruses infecting the same cell.
Smith
P D
PD
Cellular Immunology Section, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.
Saini
S S
SS
Raffeld
M
M
Manischewitz
J F
JF
Wahl
S M
SM
D003092:Colitis / Q000382:microbiology; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha