Modulation of lipopolysaccharide receptor expression by lactate dehydrogenase-elevating virus

Abstract

Lactate dehydrogenase-elevating virus (LDV) exacerbates mouse susceptibility to endotoxin shock through enhanced tumour necrosis factor (TNF) production by macrophages exposed to lipopolysaccharide (LPS). However, the in vivo enhancement of TNF production in response to LPS induced by the virus largely exceeds that found in vitro with cells derived from infected animals. Infection was followed by a moderate increase of Toll-like receptor (TLR)-4/MD2, but not of membrane CD14 expression on peritoneal macrophages. Peritoneal macrophages from LDVinfected mice unresponsive to type I interferons (IFNs) did not show enhanced expression of TLR-4/MD2 nor of CD14, and did not produce more TNF in response to LPS than cells from infected normal counterparts, although the in vivo response of these animals to LPS was strongly enhanced. In contrast, the virus triggered a sharp increase of soluble CD14 and of LPS-binding protein serum levels in normal mice. However, production of these LPS soluble receptors was similar in LDV-infected type I IFN-receptor deficient mice and in their normal counterparts. Moreover, serum of LDV-infected mice that contained these soluble receptors had little effect if any on cell response to LPS. These results suggest that enhanced response of LDV-infected mice to LPS results mostly from mechanisms independent of LPS receptor expression.

Modulation of the host microenvironment by a common non-oncolytic mouse virus leads to inhibition of plasmacytoma development through NK cell activation

“…As a result, LDV infection provides a unique model to analyse the consequences of a viral infection on the course of concomitant diseases, through alterations of the host immune microenvironment. For instance, LDV-induced activation of non-infected macrophages by cytokines that include IFN-γ leads to exacerbated sensitivity to endotoxin shock (Le-Thi-Phuong et al , 2007a; Su et al , 2012) and to enhanced autoantibody pathogenicity, followed by severe anaemia or thrombocytopenia (Meite et al , 2000; Musaji et al , 2004).…”

Degenerative Myelopathy and Neuropathy in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) Mice Caused by Lactate Dehydrogenase–Elevating Virus (LDV)

“…Immunomodulatory effects of LDV infection include nonspecific polyclonal activation of B cells, immunoglobulin secretion, acute lymphopenia, chronic lymphocytosis, and abnormal interferon and natural killer (NK) cell responses. [2][3][4]6,19,20 Reported impacts of LDV infection on other mouse models include increased susceptibility to LPSinduced septic shock, 21,22 suppression of immune-mediated islet cell injury in non-obese diabetic (NOD) mice by interfering with function of 1a-positive macrophages, 23 and antibodymediated thrombocytopenia, 24 among others.…”

Involvement of Fcα/μ Receptor in IgM Anti-Platelet, but Not Anti–Red Blood Cell Autoantibody Pathogenicity in Mice

“…Interestingly, a similar observation that the virus can increase a receptor-dependent macrophage function without modification of this receptor expression was made with the response to LPS. Indeed, LDV induces a strong enhancement of TNF production in response to LPS that does not correlate with an equal increase of the expression of TLR-4 and CD14 on responding macrophages (32,33). To explain the exacerbating effect of LDV infection on IgM autoantibody-mediated thrombocytopenia, it must therefore be postulated that the virus interferes with intracellular events in the macrophage that will enhance uptake of opsonized thrombocytes via an Fca/mR-independent mechanism.…”