Distinct gamma interferon-production pathways in mice infected with lactate dehydrogenase-elevating virus

Le-Thi-Phuong, Thao; Thirion, Gaëtan; Coutelier, Jean‐Paul

doi:10.1099/vir.0.83242-0

Cited by 15 publications

(17 citation statements)

References 13 publications

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“…Consistent with the results from pDC depletions, LDV plasma titers were again not significantly different in the absence of TLR7 expression and IFNa production ( Figure 4C). These results are similar to data from type I interferon receptor-deficient mice infected with LDV, although that study noted slight (two fold) increases in virus titers in the absence of type I interferon signaling [31].…”

Section: Resultssupporting

confidence: 87%

Lactate Dehydrogenase-Elevating Virus Induces Systemic Lymphocyte Activation via TLR7-Dependent IFNα Responses by Plasmacytoid Dendritic Cells

et al. 2009

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BackgroundLactate dehydrogenase-elevating virus (LDV) is a natural infectious agent of mice. Like several other viruses, LDV causes widespread and very rapid but transient activation of both B cells and T cells in lymphoid tissues and the blood. The mechanism of this activation has not been fully described and is the focus of the current studies.Principal FindingsA known inducer of early lymphocyte activation is IFNα, a cytokine strongly induced by LDV infection. Neutralization of IFNα in the plasma from infected mice ablated its ability to activate lymphocytes in vitro. Since the primary source of virus-induced IFNα in vivo is often plasmacytoid dendritic cells (pDC's), we depleted these cells prior to LDV infection and tested for lymphocyte activation. Depletion of pDC's in vivo eradicated both the LDV-induced IFNα response and lymphocyte activation. A primary receptor in pDC's for single stranded RNA viruses such as LDV is the toll-like receptor 7 (TLR7) pattern recognition receptor. Infection of TLR7-knockout mice revealed that both the IFNα response and lymphocyte activation were dependent on TLR7 signaling in vivo. Interestingly, virus levels in both TLR7 knockout mice and pDC-depleted mice were indistinguishable from controls indicating that LDV is largely resistant to the systemic IFNα response.ConclusionResults indicate that LDV-induced activation of lymphocytes is due to recognition of LDV nucleic acid by TLR7 pattern recognition receptors in pDC's that respond with a lymphocyte-inducing IFNα response.

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Section: Resultssupporting

confidence: 87%

Lactate Dehydrogenase-Elevating Virus Induces Systemic Lymphocyte Activation via TLR7-Dependent IFNα Responses by Plasmacytoid Dendritic Cells

et al. 2009

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“…Of note, although the number of cDC completely normalized two weeks after infection, donor T cells persisted without inducing a delayed GVHD reaction. Moreover, LDV infection performed one week after B6 spleen cell transplantation no longer impaired GVHD further supporting the action of the virus on the initiating steps of the response.…”

Section: Discussionmentioning

confidence: 76%

Mouse nidovirus LDV infection alleviates graft versus host disease and induces type I IFN-dependent inhibition of dendritic cells and allo-responsive T cells

Gaignage

Marillier

Uyttenhove

et al. 2017

Immunity, Inflammation and Disease

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IntroductionViruses have developed multiple mechanisms to alter immune reactions. In 1969, it was reported that lactate dehydrogenase‐elevating virus (LDV), a single stranded positive sense mouse nidovirus, delays skin allograft rejection and inhibits spleen alterations in graft versus host disease (GVHD). As the underlying mechanisms have remained unresolved and given the need for new therapies of this disease, we reassessed the effects of the virus on GVHD and tried to uncover its mode of action.MethodsGVHD was induced by transfer of parent (B6) spleen cells to non‐infected or LDV‐infected B6D2F1 recipients. In vitro mixed‐lymhocyte culture (MLC) reactions were used to test the effects of the virus on antigen‐presenting cells (APC) and responder T cells.ResultsLDV infection resulted in a threefold increase in survival rate with reduced weight loss and liver inflammation but with the establishment of permanent chimerism that correlated with decreased interleukine (IL)‐27 and interferon (IFN)γ plasma levels. Infected mice showed a transient elimination of splenic CD11b+ and CD8α+ conventional dendritic cells (cDCs) required for allogeneic CD4 and CD8 T cell responses in vitro. This drop of APC numbers was not observed with APCs derived from toll‐like receptor (TLR)7‐deficient mice. A second effect of the virus was a decreased T cell proliferation and IFNγ production during MLC without detectable changes in Foxp3+ regulatory T cell (Tregs) numbers. Both cDC and responder T cell inhibition were type I IFN dependent. Although the suppressive effects were very transient, the GVHD inhibition was long‐lasting.ConclusionA type I IFN‐dependent suppression of DC and T cells just after donor spleen cell transplantation induces permanent chimerism and donor cell implantation in a parent to F1 spleen cell transplantation model. If this procedure can be extended to full allogeneic bone marrow transplantation, it could open new therapeutic perspectives for hematopoietic stem cell transplantation (HSCT).

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“…Mouse LDV infection activated NK cells, leading to enhanced cytotoxicity and IFN-c production. 13,15 CD66a expression on NK cells was therefore analysed after LDV infection. One day after infection, a moderate increase in the proportion of CD49b + cells was observed in the liver (Fig.…”

Section: Cd66a Expression On Activated Mouse Nk Cellsmentioning

confidence: 99%

CD66a (CEACAM1) expression by mouse natural killer cells

2008

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Summary CD66a (CEACAM1), an adhesion molecule that has regulatory function on T lymphocytes, was found to be expressed on a minority of mouse natural killer (NK) cells, especially in the liver. CD66a expression on NK cells depended on their differentiation stage, with highest levels on immature CD49b−NK cells. Expression of CD66a on NK cells was strongly enhanced by in vitro activation with interleukin‐12 (IL‐12) and IL‐18. However, in vivo NK cell stimulation by infection with lactate dehydrogenase‐elevating virus did not lead to strong CD66a expression, even on activated interferon‐‐γ‐producing NK cells. These results indicate that CD66a expression is differently regulated, depending on the NK cell activation pathway, which may lead to distinct regulatory mechanisms of the functional subpopulations of these cells.

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Distinct gamma interferon-production pathways in mice infected with lactate dehydrogenase-elevating virus

Cited by 15 publications

References 13 publications

Lactate Dehydrogenase-Elevating Virus Induces Systemic Lymphocyte Activation via TLR7-Dependent IFNα Responses by Plasmacytoid Dendritic Cells

Lactate Dehydrogenase-Elevating Virus Induces Systemic Lymphocyte Activation via TLR7-Dependent IFNα Responses by Plasmacytoid Dendritic Cells

Mouse nidovirus LDV infection alleviates graft versus host disease and induces type I IFN-dependent inhibition of dendritic cells and allo-responsive T cells

CD66a (CEACAM1) expression by mouse natural killer cells

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