Tumor necrosis factor alpha and macrophages in the brain of herpes simplex virus type 1-infected BALB/c mice.
After uniocular anterior chamber (AC) inoculation of herpes simplex virus type 1 (HSV-1), virus and TNF alpha (TNF-alpha) are detected in the suprachiasmatic nuclei (SCN). The goal of this study was to investigate the role of TNF-alpha and macrophages in the brain of HSV-1-infected BALB/c mice. Mice were treated with thalidomide for TNF-alpha inhibition or injected with clodronate liposomes to deplete macrophages, and the AC of one eye (ipsilateral) was injected with HSV-1 (KOS). The location of HSV-1, macrophages, and TNF-alpha was determined by fluorescence immunohistochemistry and the titer of virus was determined by plaque assay. Inhibition of TNF-alpha was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and depletion of macrophages was assessed by flow cytometry. In thalidomide-treated mice, TNF-alpha RNA levels were reduced in the SCN. Both SCN were infected by day 5 post inoculation (p.i.) and the titer of virus in the SCN contralateral to the side of injection was increased. The number of splenic macrophages was significantly reduced in clodronate-treated mice compared with controls. In macrophage-depleted mice, both SCN were infected at day 6 p.i. and the titer of virus in the SCN of these mice was increased at days 6 and 7 p.i. compared with controls. The titer of virus in the contralateral (uninoculated) eye of macrophage-depleted mice was increased at day 7 p.i. Fewer F4/80+ cells were observed in the SCN of macrophage-depleted mice. The results of these studies suggest that TNF-alpha plays a role in limiting virus replication in the SCN of euthymic BALB/c mice and that one source of TNF-alpha is macrophages.
Fields
Mark
M
Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, Georgia 30912, USA.
Zheng
Mei
M
Zhang
Ming
M
Atherton
Sally S
SS
D000818:Animals; D001921:Brain / Q000276:immunology / Q000821:virology*; D004002:Clodronic Acid / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000502:physiology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013792:Thalidomide / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism*
D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004002:Clodronic Acid; D013792:Thalidomide