ABSTRACT
Measles virus (MV) infects CD150Tg/Ifnar (IFN alpha receptor)(-/-) mice but not CD150 (a human MV receptor)-transgenic (Tg) mice. We have shown that bone marrow-derived dendritic cells (BMDCs) from CD150Tg/Ifnar(-/-) mice are permissive to MV in contrast to those from simple CD150Tg mice, which reveals a crucial role of type I interferon (IFN) in natural tropism against MV. Yet, the mechanism whereby BMDCs produce initial type I IFN has not been elucidated in MV infection. RNA virus infection usually allows cells to generate double-stranded RNA and induce activation of IFN regulatory factor (IRF) 3/7 transcription factors, leading to the production of type I IFN through the retinoic acid-inducible gene I (RIG-I)/melanoma differentiation-associated gene 5 (MDA5)-mitochondrial antiviral signaling protein (MAVS) pathway. In mouse experimental BMDCs models, we found CD150Tg/Mavs(-/-)BMDCs, but not CD150Tg/Irf3(-/-)/Irf7(-/-)BMDCs, permissive to MV. IFN-α/ß were not induced in MV-infected CD150Tg/Mavs(-/-)BMDCs, while IFN-ß was subtly induced in CD150Tg/Irf3(-/-)/Irf7(-/-)BMDCs. In vivo systemic infection was therefore established by transfer of MV-infected CD150Tg/Mavs(-/-) BMDCs to CD150Tg/Ifnar(-/-) mice. These data indicate that MAVS-dependent, IRF3/7-independent IFN-ß induction triggers the activation of the IFNAR pathway so as to restrict the spread of MV by infected BMDCs. Hence, MAVS participates in the initial induction of type I IFN in BMDCs and IFNAR protects against MV spreading. We also showed the importance of IL-10-producing CD4(+) T cells induced by MV-infected BMDCs in vitro, which may account for immune modulation due to the functional aberration of DCs.
Subject(s)
Dendritic Cells/immunology , Interferon Regulatory Factor-3/genetics , Interferon Regulatory Factor-7/genetics , Interferon-beta/metabolism , Measles/immunology , Adaptor Proteins, Signal Transducing/deficiency , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Vesicular Transport/deficiency , Adaptor Proteins, Vesicular Transport/genetics , Animals , Antigens, CD/metabolism , Bone Marrow Cells/cytology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Cell Line , Chlorocebus aethiops , DEAD Box Protein 58 , DEAD-box RNA Helicases/metabolism , Dendritic Cells/cytology , Interferon Regulatory Factor-3/deficiency , Interferon Regulatory Factor-3/metabolism , Interferon Regulatory Factor-7/deficiency , Interferon Regulatory Factor-7/metabolism , Interferon-Induced Helicase, IFIH1 , Interferon-beta/biosynthesis , Interleukin-10/metabolism , Measles virus/immunology , Mice , Mice, Inbred C57BL , Mice, Knockout , Receptor, Interferon alpha-beta/genetics , Receptors, Cell Surface/metabolism , Signal Transduction/immunology , Signaling Lymphocytic Activation Molecule Family Member 1 , Vero CellsABSTRACT
We present the non-contrast-enhanced CT finding of high attenuation within metastatic regional lymph nodes in two patients with stage I or II tongue carcinoma during a follow-up period. The attenuation values of these lesions were approximately 70 HU or more. One patient had a level I node, and the other had a level II node. Contrast-enhanced CT failed to reveal these hyperattenuated areas within the nodes. Histopathologic examination revealed that these hyperattenuated areas were strongly correlated with the area of marked keratinization of metastatic foci. If contrast-enhanced CT had been the only imaging technique used, these lesions might have been overlooked. The clinician should be aware of the characteristic findings of non-contrast-enhanced, as well as contrast-enhanced, CT when investigating lymph node metastases at an early stage in patients with stage I or II tongue carcinoma during the follow-up period.
