Human T-cell leukemia virus type I infection of monocytes and microglial cells in primary human cultures.
The pathogenesis of progressive spastic paraparesis [HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP)], a serious consequence of human T-cell leukemia virus type I (HTLV-I) infection, is unclear. T and B lymphocytes can be naturally infected by HTLV-I, but the susceptibility to HTLV-I infection of other cell types that could contribute to the pathogenesis of HAM/TSP has not been determined. We found that a human monocyte cell line (THP-1), primary human peripheral blood monocytes, and isolated microglial cells but not astrocytes or oligodendroglial cells derived from adult human brain were infected by HTLV-I in vitro. Infection with HTLV-I enhanced the secretion of interleukin 6 in human microglial cell-enriched cultures but did not stimulate the release of interleukin 1 from monocytes or microglial cells. Tumor necrosis factor alpha production was stimulated by HTLV-I infection of monocytes and microglial cells and could be enhanced by suboptimal amounts of lipopolysaccharide. Since both tumor necrosis factor alpha and interleukin 6 have been implicated in inflammatory demyelination and gliosis, our findings suggest that human microglial cells and monocytes infected with and activated by HTLV-I could play a role in the pathogenesis of HAM/TSP.
Hoffman
P M
PM
Retrovirus Research Center, Department of Veterans Affairs Medical Center, Baltimore, MD 21218.
Dhib-Jalbut
S
S
Mikovits
J A
JA
Robbins
D S
DS
Wolf
A L
AL
Bergey
G K
GK
Lohrey
N C
NC
Weislow
O S
OS
Ruscetti
F W
FW
D001921:Brain / Q000382:microbiology; D002478:Cells, Cultured; D015490:HTLV-I Infections / Q000382:microbiology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000096:biosynthesis; D009000:Monocytes / Q000382:microbiology*; D009457:Neuroglia / Q000382:microbiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012367:RNA, Viral / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015850:Interleukin-6; D012333:RNA, Messenger; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha