Host–Virus Interactions during Malaria Infection in Hepatitis B Virus Transgenic Mice

Pasquetto, Valérie; Guidotti, Luca G.; Kakimi, Kazuhiro; Tsuji, Moriya; Chisari, Francis V.

doi:10.1084/jem.192.4.529

Cited by 61 publications

(55 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, in the case of hepatitis B virus-Tg mice, malaria-induced proinflammatory cytokines have the opposite role, causing the suppression of hepatitis B virus replication and gene expression, emphasizing the distinct mechanisms regulating transgene expression in these two viral models (38).…”

Section: Discussionmentioning

confidence: 99%

In Vivo CD40-CD154 (CD40 Ligand) Interaction Induces Integrated HIV Expression by APC in an HIV-1-Transgenic Mouse Model

Chougnet

Freitag

Schito

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

Because of their relative resistance to viral cytopathic effects, APC can provide an alternative reservoir for latently integrated HIV. We used an HIV-transgenic mouse model in which APC serve as the major source of inducible HIV expression to study mechanisms by which integrated virus can be activated in these cells. When admixed with transgenic APC, activated T lymphocytes provided a major contact-dependent stimulus for viral protein expression in vitro. Using blocking anti-CD154 mAb as well as CD154-deficient T cells, the HIV response induced by activated T lymphocytes was demonstrated to require CD40-CD154 interaction. The role of this pathway in the induction of HIV expression from APC in vivo was further studied in an experimental model involving infection of the HIV-transgenic mice with Plasmodium chabaudi parasites. Enhanced viral production by dendritic cells and macrophages in infected mice was associated with up-regulated CD40 expression. More importantly, in vivo treatment with blocking anti-CD154 mAb markedly reduced viral expression in P. chabaudi-infected animals. Together, these findings indicate that immune activation of integrated HIV can be driven by the costimulatory interaction of activated T cells with APC. Because chronic T cell activation driven by coinfections as well as HIV-1 itself is a characteristic of HIV disease, this pathway may be important in sustaining viral expression from APC reservoirs.

show abstract

Section: Discussionmentioning

confidence: 99%

In Vivo CD40-CD154 (CD40 Ligand) Interaction Induces Integrated HIV Expression by APC in an HIV-1-Transgenic Mouse Model

Chougnet

Freitag

Schito

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…However, activated NK cells in some cases are not involved in liver injury, as reported in ConAinduced hepatitis or a-GalCer-induced liver injury [15][16][17]. In HBV transgenic mice, activated NK cells caused liver injury when inhibiting HBV replication [18][19][20][21][22]. However, Guidotti et al demonstrated that activated NK cells contributed to viral clearance without any cytopathic effects on liver in the HBV-infected chimpanzee [23].…”

Section: Introductionmentioning

confidence: 99%

Liver-specific HBsAg transgenic mice are over-sensitive to Poly(I:C)-induced liver injury in NK cell- and IFN-γ-dependent manner

Chen

Sun

Jiang

et al. 2007

Journal of Hepatology

View full text Add to dashboard Cite

Background/Aims: The role of natural killer (NK) cells in the development of hepatitis B virus (HBV)-associated liver injury remains obscure. In this study, we elucidated the role of NK cells in liver injury of HBsAg transgenic mice (HBs-B6), a mimic of human healthy chronic HBsAg carriers, triggered by polyinosinic:polycytidylic acid [Poly(I:C)].Methods: HBs-B6 or wild B6 mice were intraperitoneally injected with Poly(I:C) at different doses. Liver injury was evaluated by serum transaminase activity and histopathologic changes.Results: HBs-B6 mice were over-sensitive to Poly(I:C)-induced liver injury, which was absolutely dependent on the presence of NK cells and IFN-c produced by intrahepatic NK cells. Much stronger IFN-c receptor expression was observed on hepatocytes of HBs-B6 mice, which was significantly enhanced by Poly(I:C) injection. Treatment with IFN-c in vitro triggered much higher activation of downstream signals (pSTAT1-IRF-1) in hepatocytes of HBs-B6 mice. Depletion of Kupffer cells and neutralization of endogenous IL-12 did not affect Poly(I:C)-induced over-sensitive liver injury in HBs-B6 mice.Conclusions: NK cells played a critical role in an IFN-c dependent, Kupffer cell-and IL-12-independent manner in oversensitive liver injury triggered by Poly(I:C) in murine chronic HBsAg carriers. Ó

show abstract

“…Enhanced NK cell activity in spleens of mice infected with irradiated Plasmodium berghei sporozoites was demonstrated many years ago (17); more recently, Plasmodium yoelii sporozoite infection has been shown to induce a rapid inflammatory response in the liver characterized by NK cell, macrophage, and T cell infiltration and IFN-␥ production (18). It has been proposed that protective immunity to P. yoelii liver stages mediated by parasite-specific CD8 ϩ T cells is dependent on the presence of IL-12 and NK cells (19), indicating an important synergy between innate and adaptive immunity in this system.…”

mentioning

confidence: 99%

Innate Immune Response to Malaria: Rapid Induction of IFN-γ from Human NK Cells by LivePlasmodium falciparum-Infected Erythrocytes

Artavanis‐Tsakonas

Riley

2002

The Journal of Immunology

283

247

View full text Add to dashboard Cite

To determine the potential contribution of innate immune responses to the early proinflammatory cytokine response to Plasmodium falciparum malaria, we have examined the kinetics and cellular sources of IFN-γ production in response to human PBMC activation by intact, infected RBC (iRBC) or freeze-thaw lysates of P. falciparum schizonts. Infected erythrocytes induce a more rapid and intense IFN-γ response from malaria-naive PBMC than do P. falciparum schizont lysates correlating with rapid iRBC activation of the CD3−CD56+ NK cell population to produce IFN-γ. IFN-γ+ NK cells are detectable within 6 h of coculture with iRBC, their numbers peaking at 24 h in most donors. There is marked heterogeneity between donors in magnitude of the NK-IFN-γ response that does not correlate with mitogen- or cytokine-induced NK activation or prior malaria exposure. The NK cell-mediated IFN-γ response is highly IL-12 dependent and appears to be partially IL-18 dependent. Exogenous rIL-12 or rIL-18 did not augment NK cell IFN-γ responses, indicating that production of IL-12 and IL-18 is not the limiting factor explaining differences in NK cell reactivity between donors or between live and dead parasites. These data indicate that NK cells may represent an important early source of IFN-γ, a cytokine that has been implicated in induction of various antiparasitic effector mechanisms. The heterogeneity of this early IFN-γ response between donors suggests a variation in their ability to mount a rapid proinflammatory cytokine response to malaria infection that may, in turn, influence their innate susceptibility to malaria infection, malaria-related morbidity, or death from malaria.

show abstract

Host–Virus Interactions during Malaria Infection in Hepatitis B Virus Transgenic Mice

Cited by 61 publications

References 50 publications

In Vivo CD40-CD154 (CD40 Ligand) Interaction Induces Integrated HIV Expression by APC in an HIV-1-Transgenic Mouse Model

In Vivo CD40-CD154 (CD40 Ligand) Interaction Induces Integrated HIV Expression by APC in an HIV-1-Transgenic Mouse Model

Liver-specific HBsAg transgenic mice are over-sensitive to Poly(I:C)-induced liver injury in NK cell- and IFN-γ-dependent manner

Innate Immune Response to Malaria: Rapid Induction of IFN-γ from Human NK Cells by LivePlasmodium falciparum-Infected Erythrocytes

Contact Info

Product

Resources

About