Loss of mandibular lymph node integrity is associated with an increase in sensitivity to HSV-1 infection in CD118-deficient mice.
Type I IFNs are potent antiviral cytokines that contribute to the development of the adaptive immune response. To determine the role of type I IFNs in this process in an infectious disease model, mice deficient in the type I IFN receptor (CD118(-/-)) were ocularly infected with HSV-1 and surveyed at times post infection in the nervous system and lymph node for virus and the host immune response. Virus titers were elevated in the trigeminal ganglia and brain stem with virus disseminating rapidly to the draining lymph node of CD118(-/-) mice. T cell and plasmacytoid dendritic cell infiltration into the brain stem was reduced in CD118(-/-) mice following infection, which correlated with a reduction in CXCL10 but not CXCL9 expression. In contrast, CXCL1 and CCL2 levels were up-regulated in the brainstem of CD118(-/-) mice associated with an increase in F4/80(+) macrophages. By day 5 post infection, there was a significant loss in T, NK, and plasmacytoid dendritic cell numbers in the draining lymph nodes associated with an increase in apoptotic/necrotic T cells and an appreciable lack of HSV-specific CD8(+) T cells. The adoptive transfer of HSV-specific TCR transgenic CD8(+) T cells into CD118(-/-) mice at the time of infection modestly reduced viral titers in the nervous system suggesting in addition to the generation of HSV-specific CD8(+) T cells, other type I IFN-activated pathways are instrumental in controlling acute infection.
Conrady
Christopher D
CD
Department of Microbiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Thapa
Manoj
M
Wuest
Todd
T
Carr
Daniel J J
DJ
D000818:Animals; D001933:Brain Stem / Q000276:immunology / Q000473:pathology / Q000821:virology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D006561:Herpes Simplex / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D018259:Herpesvirus 1, Human / Q000276:immunology*; D007113:Immunity, Innate / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology / Q000821:virology; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit / Q000172:deficiency* / Q000235:genetics; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D008297:Male; D008334:Mandible / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012668:Trigeminal Ganglion / Q000276:immunology / Q000473:pathology / Q000821:virology; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
D053680:Leukemia Inhibitory Factor Receptor alpha Subunit