Nuclear accumulation of interferon gamma.

Bader, Thomas; Weitzerbin, J

doi:10.1073/pnas.91.25.11831

Cited by 71 publications

(45 citation statements)

References 37 publications

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“…1). Bipartite nuclear localization signals are known to be necessary for nuclear targeting (5,19,44,63). Interestingly, the same motif is present in almost one-half the nuclear proteins in the Swiss protein database but in less than 5% of the nonnuclear proteins, and many of these proteins are secreted or targeted to other organelles.…”

Section: Resultsmentioning

confidence: 99%

Expression of a Novel Leishmania Gene Encoding a Histone H1-Like Protein in Leishmania major Modulates Parasite Infectivity In Vitro

Papageorgiou

Soteriadou

2002

Infect Immun

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We describe identification and characterization of a novel two-copy gene of the parasitic protozoan Leishmania that encodes a nuclear protein designated LNP18. This protein is highly conserved in the genus Leishmania, and it is developmentally regulated. It is an alanine-and lysine-rich protein with potential bipartite nuclear targeting sequence sites. LNP18 shows sequence similarity to H1 histones of trypanosomatids and of higher eukaryotes and in particular with histone H1 of Leishmania major. The nuclear localization of LNP18 was determined by indirect immunofluorescence and Western blot analysis of isolated nuclei by using antibodies raised against the recombinant protein as probes. The antibodies recognized predominantly a 18-kDa band or a 18-kDa-16-kDa doublet. Photochemical cross-linking of intact parasites followed by Western blot analysis provided evidence that LNP18 is indeed a DNA-binding protein. Generation of transfectants overexpressing LNP18 allowed us to determine the role of this protein in Leishmania infection of macrophages in vitro. These studies revealed that transfectants overexpressing LNP18 are significantly less infective than transfectants with the vector alone and suggested that the level of LNP18 expression modulates Leishmania infectivity, as assessed in vitro.Leishmania spp. are obligately intracellular protozoan parasites that are members of the family Trypanosomatidae, and they cause a wide spectrum of human diseases of major health importance, ranging from self-healing cutaneous lesions to severe visceral leishmaniasis or kala-azar with a high fatality rate (13). These parasites have two developmentally distinct stages; the amastigotes are nonmotile forms that survive and replicate within mammalian host macrophages, and the motile flagellated promastigotes survive and replicate inside the insect vector (13

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Section: Resultsmentioning

confidence: 99%

Expression of a Novel Leishmania Gene Encoding a Histone H1-Like Protein in Leishmania major Modulates Parasite Infectivity In Vitro

Papageorgiou

Soteriadou

2002

Infect Immun

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“…Interferon γ exerts its effects on the surface of target cells through interaction with a specific receptor complex. When IFN-γ is bound, the receptor complex is itself rapidly transported to the nucleus via receptor-mediated endocytosis (35). Antibodies can be used to observe internal IFN-γ for at least 40 min (36).…”

Section: Discussionmentioning

confidence: 99%

Cd4-Expressing Cells Are Early Mediators of the Innate Immune System During Sepsis

Martignoni

Tschöp²,

Goetzman³

et al. 2008

Shock

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It is well established that the immune response to sepsis is mediated by leukocytes associated with the innate immune system. However, there is an emerging view that T lymphocytes can also mediate this response. Here, we observed a significant depletion of both CD4 and CD8 T cells in human patients after blunt trauma. To determine what effect the loss of these cells may have during a subsequent infection, we obtained CD4-and CD8-deficient mice and subjected them to cecal ligation and puncture (CLP). We observed that CD4 knockout (KO) mice showed increased CLP-induced mortality compared with CD8-deficient and wild-type (WT) mice especially within the first 30 h of injury. CD4 KO mice also exhibited significantly increased IL-6 concentrations after the CLP. The CD4 KO mice had an increased concentration of bacteremia as compared with WT mice. Antibiotic treatment decreased mortality in the CD4 KO mice as compared with no changes in the wild mice after CLP. Neutrophils isolated from septic CD4 KO mice showed decreased spontaneous oxidative burst compared with neutrophils taken from septic controls. We examined the role of IFN-γ by using mice deficient in this cytokine and found these mice to have significantly higher mortality as compared with WT mice. Finally, we detected a 2-fold increase in CD11b + cells that exhibited intracellular IFN-γ staining in the peritoneum of WT mice after CLP. The data suggest that CD4 + cells may facilitate the early clearance of bacteria by regulating neutrophils function possibly through an IFN-γ-dependent mechanism.

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“…Nuclei from cells grown in 162-cm 2 flasks were isolated using a centrifugation method as previously described (22). Nuclei were washed in centrifugation buffer, lysed, and analyzed as described previously (20).…”

Section: Nuclear Translocation Of Ifn-␥mentioning

confidence: 99%

Lipid Microdomains Are Required Sites for the Selective Endocytosis and Nuclear Translocation of IFN-γ, Its Receptor Chain IFN-γ Receptor-1, and the Phosphorylation and Nuclear Translocation of STAT1α

Subramaniam

Johnson

2002

The Journal of Immunology

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IFN-γ contains a nuclear localization sequence that may play a role in the nuclear transport of activated STAT1α via a complex of IFN-γ/IFN-γ receptor (IFNGR)-1/STAT1α with the nuclear importer nucleoprotein interactor 1. In this study, we examine the mechanism of endocytosis of IFNGR-1 and the relationship of its nuclear translocation to that of STAT1α. In untreated WISH cells, both IFNGR-1 and IFNGR-2 were constitutively localized within caveolae-like microdomains isolated from plasma membrane. However, treatment of cells with IFN-γ resulted in rapid migration of IFNGR-1, but not IFNGR-2, from these microdomains. Filipin pretreatment, which specifically inhibits endocytosis from caveolae-like microdomains, inhibited the nuclear translocation of IFN-γ and IFNGR-1 as well as the tyrosine phosphorylation and nuclear translocation of STAT1α, but did not affect the binding of IFN-γ to these cells. In the Jurkat T lymphocyte cell line, which does not express caveolin-1, nuclear translocation of IFNGR-1 and STAT1α were similarly inhibited by filipin pretreatment. Isolation of lipid microdomains from Jurkat cells showed that both IFNGR-1 and IFNGR-2 were associated with lipid microdomains only after stimulation with IFN-γ, suggesting that the IFNGR subunits are recruited to lipid microdomains by IFN-γ binding in lymphocytes (Jurkat) in contrast to their constitutive presence in epithelial (WISH) cells. In contrast, treatments that block clathrin-dependent endocytosis did not inhibit either activation or nuclear translocation of STAT1α or the nuclear translocation of IFN-γ or IFNGR-1. Thus, membrane lipid microdomains play an important role in IFN-γ-initiated endocytic events involving IFNGR-1, and the nuclear translocation of IFN-γ, IFNGR-1, and STAT1α.

show abstract

Nuclear accumulation of interferon gamma.

Cited by 71 publications

References 37 publications

Expression of a Novel Leishmania Gene Encoding a Histone H1-Like Protein in Leishmania major Modulates Parasite Infectivity In Vitro

Expression of a Novel Leishmania Gene Encoding a Histone H1-Like Protein in Leishmania major Modulates Parasite Infectivity In Vitro

Cd4-Expressing Cells Are Early Mediators of the Innate Immune System During Sepsis

Lipid Microdomains Are Required Sites for the Selective Endocytosis and Nuclear Translocation of IFN-γ, Its Receptor Chain IFN-γ Receptor-1, and the Phosphorylation and Nuclear Translocation of STAT1α

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