Herpes simplex virus type 2-induced mortality following genital infection is blocked by anti-tumor necrosis factor alpha antibody in CXCL10-deficient mice.
The role of tumor necrosis factor alpha (TNF-alpha) was evaluated for CXCL10-deficient (CXCL10(-/-)) mice which succumbed to genital herpes simplex virus type 2 (HSV-2) infection and possessed elevated levels of virus and TNF-alpha but not other cytokines in the central nervous system (CNS) and vaginal tissue within the first 7 days following virus exposure. Anti-TNF-alpha but not control antibody treatment offsets the elevated mortality rate of CXCL10(-/-) mice, despite increased CNS viral titers. In addition, TNF-alpha neutralization suppressed recruitment of leukocyte subpopulations into the CNS, which is associated with reduced CCL2 and CXCL9 expression. Collectively, the results implicate TNF-alpha as the principal mediator of mortality in response to genital HSV-2 infection.
Thapa
Manoj
M
Department of Ophthalmology, DMEI #415, University of Oklahoma Health Sciences Center, 608 Stanton L Young Blvd., Oklahoma City, OK 73104, USA.
Carr
Daniel J J
DJ
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D018931:Antineoplastic Agents, Hormonal / Q000378:metabolism; D001933:Brain Stem / Q000166:cytology / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D054357:Chemokine CXCL10 / Q000235:genetics / Q000276:immunology; D054370:Chemokine CXCL9 / Q000276:immunology; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology / Q000401:mortality; D018258:Herpesvirus 2, Human / Q000276:immunology / Q000472:pathogenicity; D017258:Medroxyprogesterone Acetate / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D013116:Spinal Cord / Q000166:cytology / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D014621:Vagina / Q000166:cytology / Q000276:immunology / Q000473:pathology
D000906:Antibodies; D018931:Antineoplastic Agents, Hormonal; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; C485969:Cxcl9 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D017258:Medroxyprogesterone Acetate