Regulatory Role of CD1d in Neurotropic Virus Infection

Abstract

The GDVII strain of Theiler's murine encephalomyelitis virus (TMEV) causes an acute fatal polioencephalomyelitis in mice. Infection of susceptible mice with the DA strain of TMEV results in an acute polioencephalomyelitis followed by chronic immune-mediated demyelination with virus persistence in the central nervous system (CNS); DA virus infection is used as an animal model for multiple sclerosis. CD1d-restricted natural killer T (NKT) cells can contribute to viral clearance and regulation of autoimmune responses. To investigate the role of CD1d in TMEV infection, we first infected CD1d-deficient mice (CD1 ؊/؊ ) and wild-type BALB/c mice with GDVII virus. Wild-type mice were more resistant to virus than CD1 ؊/؊ mice (50% lethal dose titers: wild-type mice, 10 PFU; CD1 ؊/؊ mice, 1.6 PFU). Wild-type mice had fewer viral antigen-positive cells with greater inflammation in the CNS than CD1 ؊/؊ mice. Second, an analysis of DA virus infection in CD1 ؊/؊ mice was conducted. Although both wild-type and CD1 ؊/؊ mice had similar clinical signs during the first 2 weeks after infection, CD1 ؊/؊ mice had an increase in neurological deficits over those observed in wild-type mice at 3 to 5 weeks after infection. Although wild-type mice had no demyelination, 20 and 60% of CD1 ؊/؊ mice developed demyelination at 3 and 5 weeks after infection, respectively. TMEV-specific lymphoproliferative responses, interleukin-4 (IL-4) production, and IL-4/gamma interferon ratios were higher in CD1 ؊/؊ mice than in wild-type mice. Thus, CD1d-restricted NKT cells may play a protective role in TMEV-induced neurological disease by alteration of the cytokine profile and virus-specific immune responses.

Potential Role of Invariant NKT Cells in the Control of Pulmonary Inflammation and CD8+ T Cell Response during Acute Influenza A Virus H3N2 Pneumonia

“…Teixeira, and F. Trottein, submitted for publication) infections. Studies using CD1d-deficient mice, which not only lack iNKT cells but also non-iNKT cells, have suggested that NKT cells (either iNKT cells, non-iNKT cells, or both) positively contribute to the immune response to respiratory syncytial virus (20), encephalomyocarditis virus (21), murine CMV (22), and Theiler's murine encephalomyelitis virus (23). In contrast, noniNKT cells are rather deleterious during coxsackievirus infection (24).…”

NKT cells: Friend or foe during viral infections?

“…CD1d-dependent cells are involved in controlling the infection in the CNS, as shown by the higher viral load in Cd1d À/À mice. This increased viral load is probably due to a defective local immune response, as few infiltrating immune cells are detected in the CNS of Cd1d À/À mice [47]. Interestingly, studies of CD1d-deficient mice suggest that NKT cells could modulate the IFN-g/IL-4 balance during infection with the TMEV DA strain, which induces acute disease followed by chronic immune-mediated demyelination with virus persistence in the CNS.…”

T Cell-, Interleukin-12-, and Gamma Interferon-Driven Viral Clearance in Measles Virus-Infected Brain Tissue

“…However, with the increase in the number of immunocompromised individuals, whether through increasing populations of AIDS patients or pharmacologically compromised tissue transplant recipients, there has been a concomitant increase in viral encephalitis (11,77). Some viral infections, rather than being cleared by the host's immune system, result instead in high morbidity or mortality, often accompanied by severe inflammation (18,68,81). The balance between whether the adaptive immune response to a specific viral infection is protective or harmful is delicate, as many of the mechanisms that mediate inflammation in the CNS in both settings are similar (6,12,31,65).…”