Perforin and Gamma Interferon-Mediated Control of Coronavirus Central Nervous System Infection by CD8 T Cells in the Absence of CD4 T Cells

Bergmann, Cornelia C.; Parra, Beatriz; Hinton, David R.; Ramakrishna, Chandran; Dowdell, Konechi C.; Stohlman, Stephen A.

doi:10.1128/jvi.78.4.1739-1750.2004

Cited by 101 publications

(177 citation statements)

References 42 publications

(133 reference statements)

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“…Antibodies seem to play a prominent role in the case of neuronal infection with Theiler's murine encephalitis virus (19), the neurotropic JHM variant of mouse hepatitis virus (17), Sindbis virus (8,37), and rabies virus (51). A contribution of IFN-␥ in viral clearance from neurons has previously been noted in a number of neurotropic virus infections, including vaccinia virus and vesicular stomatitis virus (35,36), measles virus (49,69), neurotropic mouse hepatitis virus (7,48,50), Sindbis virus (8), and lymphocytic choriomeningitis virus (65). However, the strict and exclusive dependence of BDV resistance on IFN-␥ during primary and secondary immune responses is unique.…”

Section: Discussionmentioning

confidence: 99%

CD8 T Cells Require Gamma Interferon To Clear Borna Disease Virus from the Brain and Prevent Immune System-Mediated Neuronal Damage

Hausmann¹,

Pagenstecher

Baur³

et al. 2005

J Virol

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Borna disease virus (BDV) frequently causes meningoencephalitis and fatal neurological disease in young but not old mice of strain MRL. Disease does not result from the virus-induced destruction of infected neurons. Rather, it is mediated by H-2 k -restricted antiviral CD8 T cells that recognize a peptide derived from the BDV nucleoprotein N. Persistent BDV infection in mice is not spontaneously cleared. We report here that N-specific vaccination can protect wild-type MRL mice but not mutant MRL mice lacking gamma interferon (IFN-␥) from persistent infection with BDV. Furthermore, we observed a significant degree of resistance of old MRL mice to persistent BDV infection that depended on the presence of CD8 T cells. We found that virus initially infected hippocampal neurons around 2 weeks after intracerebral infection but was eventually cleared in most wild-type MRL mice. Unexpectedly, young as well as old IFN-␥-deficient MRL mice were completely susceptible to infection with BDV. Moreover, neurons in the CA1 region of the hippocampus were severely damaged in most diseased IFN-␥-deficient mice but not in wild-type mice. Furthermore, large numbers of eosinophils were present in the inflamed brains of IFN-␥-deficient mice but not in those of wild-type mice, presumably because of increased intracerebral synthesis of interleukin-13 and the chemokines CCL1 and CCL11, which can attract eosinophils. These results demonstrate that IFN-␥ plays a central role in host resistance against infection of the central nervous system with BDV and in clearance of BDV from neurons. They further indicate that IFN-␥ may function as a neuroprotective factor that can limit the loss of neurons in the course of antiviral immune responses in the brain.

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Section: Discussionmentioning

confidence: 99%

CD8 T Cells Require Gamma Interferon To Clear Borna Disease Virus from the Brain and Prevent Immune System-Mediated Neuronal Damage

Hausmann¹,

Pagenstecher

Baur³

et al. 2005

J Virol

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“…This natural mouse pathogen is one of the most extensively studied coronaviruses (20). A strong CTL response mediates clearance of the virus between days 6 and 8 postinfection (21,22), and neutralizing Abs appear to be required to prevent re-emergence of persistent CNS infection (23,24). Nonetheless, before effective adaptive immune responses are elicited, type I IFN-mediated innate immune responses are essential for the survival of the host in the early phase of infection.…”

mentioning

confidence: 99%

Type I IFN-Mediated Protection of Macrophages and Dendritic Cells Secures Control of Murine Coronavirus Infection

Cervantes-Barragán

Kalinke

Züst

et al. 2009

The Journal of Immunology

119

135

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The swift production of type I IFNs is one of the fundamental aspects of innate immune responses against viruses. Plasmacytoid dendritic cell-derived type I IFNs are of prime importance for the initial control of highly cytopathic viruses such as the mouse hepatitis virus (MHV). The aim of this study was to determine the major target cell populations of this first wave of type I IFNs. Generation of bone marrow-chimeric mice expressing the type I IFN receptor (IFNAR) on either hemopoietic or non-bone marrow-derived cells revealed that the early control of MHV depended mainly on IFNAR expression on hemopoietic cells. To establish which cell population responds most efficiently to type I IFNs, mice conditionally deficient for the IFNAR on different leukocyte subsets were infected with MHV. This genetic analysis revealed that IFNAR expression on LysM+ macrophages and CD11c+ dendritic cells was most important for the early containment of MHV within secondary lymphoid organs and to prevent lethal liver disease. This study identifies type I IFN-mediated cross-talk between plasmacytoid dendritic cells on one side and macrophages and conventional dendritic cells on the other, as an essential cellular pathway for the control of fatal cytopathic virus infection.

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“…In contrast, IFN-c receptor-deficient animals could not be protected by a similar transfer of immune cells able to respond to this cytokine. Interestingly, after infection with MHV-JHM, CD8 lymphocytes were found to suppress MHV-JHM replication at least in oligodendroglia through IFN-c production (Bergmann et al, 2004). This cytokine was also involved in the demyelination induced by this neurotropic virus (Templeton & Perlman, 2008).…”

mentioning

confidence: 94%

“…The cellular origin of MHVinduced IFN-c has not been extensively analysed, although a few studies have indicated that either T cells (Bergmann et al, 2004;Pearce et al, 1994) or NK cells (Daniels et al, 2001) might produce this cytokine. Moreover, control of MHV pathogenicity can be mediated by an IFN-c effect on either T cells (Wijburg et al, 1996) or macrophages (Lucchiari et al, 1991).…”

mentioning

confidence: 99%

Production of protective gamma interferon by natural killer cells during early mouse hepatitis virus infection

Thirion

Coutelier

2009

Journal of General Virology

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Gamma interferon (IFN-γ) plays a major role in the protection against lethal infection with mouse hepatitis virus A59. IFN-γ production reaches a maximum level 2 days after viral inoculation, especially in liver immune cells. Among these cells, natural killer cells are the major producers of this cytokine. Transfer experiments indicated that the protective role of IFN-γ is mediated through a direct effect on cells targeted by the virus rather than through indirect activation of T lymphocytes.

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Perforin and Gamma Interferon-Mediated Control of Coronavirus Central Nervous System Infection by CD8 T Cells in the Absence of CD4 T Cells

Cited by 101 publications

References 42 publications

CD8 T Cells Require Gamma Interferon To Clear Borna Disease Virus from the Brain and Prevent Immune System-Mediated Neuronal Damage

CD8 T Cells Require Gamma Interferon To Clear Borna Disease Virus from the Brain and Prevent Immune System-Mediated Neuronal Damage

Type I IFN-Mediated Protection of Macrophages and Dendritic Cells Secures Control of Murine Coronavirus Infection

Production of protective gamma interferon by natural killer cells during early mouse hepatitis virus infection

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