Chronic innate immune activation as a cause of HIV-1 immunopathogenesis

Boasso, Adriano; Shearer, Gene M.

doi:10.1016/j.clim.2007.08.015

Cited by 173 publications

(179 citation statements)

References 75 publications

(33 reference statements)

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“…ment likely occurs in HIV-1 infection, in which prolonged activation of pDC by the virus, through a CD4/gp120 interaction, might result in long-term suppression of T cell responses and immune exhaustion through activation of IDO (33). We showed that upregulated type I IFNs in 1-MT-treated mice or IDO 2/2 mice suppress LP-BM5 virus replication (Fig.…”

Section: Discussionmentioning

confidence: 73%

The Absence of IDO Upregulates Type I IFN Production, Resulting in Suppression of Viral Replication in the Retrovirus-Infected Mouse

Hoshi¹,

Saito

Hara

et al. 2010

The Journal of Immunology

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Indoleamine 2,3-dioxygenase, the l-tryptophan–degrading enzyme, plays a key role in the powerful immunomodulatory effects on several different types of cells. Because modulation of IDO activities after viral infection may have great impact on disease progression, we investigated the role of IDO following infection with LP-BM5 murine leukemia virus. We found suppressed BM5 provirus copies and increased type I IFNs in the spleen from IDO knockout (IDO−/−) and 1-methyl-d-l-tryptophan–treated mice compared with those from wild-type (WT) mice. Additionally, the number of plasmacytoid dendritic cells in IDO−/− mice was higher in the former than in the WT mice. In addition, neutralization of type I IFNs in IDO−/− mice resulted in an increase in LP-BM5 viral replication. Moreover, the survival rate of IDO−/− mice or 1-methyl-d-l-tryptophan–treated mice infected with LP-BM5 alone or with both Toxoplasma gondii and LP-BM5 was clearly greater than the survival rate of WT mice. To our knowledge, the present study is the first report to observe suppressed virus replication with upregulated type I IFN in IDO−/− mice, suggesting that modulation of the IDO pathway may be an effective strategy for treatment of virus infection.

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Section: Discussionmentioning

confidence: 73%

The Absence of IDO Upregulates Type I IFN Production, Resulting in Suppression of Viral Replication in the Retrovirus-Infected Mouse

Hoshi¹,

Saito

Hara

et al. 2010

The Journal of Immunology

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“…During HIV infection, HIV replication leads to activation of the innate and adaptive immune systems, generating an inflammatory environment associated with the induction of type I IFN (16). The potential role of type I IFN in HIV pathogenesis and treatment has been studied since the beginning of the HIV epidemic (17).…”

Section: H Uman Immunodeficiency Virus Infection Is Characterizedmentioning

confidence: 99%

CD4 and CD8 T Cell Immune Activation during Chronic HIV Infection: Roles of Homeostasis, HIV, Type I IFN, and IL-7

Catálfamo

Wilhelm

Tcheung

et al. 2011

The Journal of Immunology

110

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Immune activation plays an important role in the pathogenesis of HIV disease. Although the causes are not fully understood, the forces that lead to immune dysfunction differ for CD4 and CD8 T cells. In this study, we report that the molecular pathways that drive immune activation during chronic HIV infection are influenced by differences in the homeostatic regulation of the CD4 and CD8 T cell pools. Proliferation of CD4 T cells is controlled more tightly by CD4 T cell numbers than is CD8 T cell proliferation. This difference reflects the importance of maintaining a polyclonal CD4 T cell pool in host surveillance. Both pools of T cells were found to be driven by viral load and its associated state of inflammation. In the setting of HIV-induced lymphopenia, naive CD4 T cells were recruited mainly into the proliferating pool in response to CD4 T cell depletion, whereas naive CD8 T cell proliferation was driven mainly by levels of HIV RNA. RNA analysis revealed increased expression of genes associated with type I IFN and common γ chain cytokine signaling in CD4 T cell subsets and only type I IFN-associated genes in CD8 T cell subsets. In vitro studies demonstrated enhanced STAT1 phosphorylation in response to IFN-α and increased expression of the IFNAR1 transcripts in naive and memory CD4 T cells compared with that observed in CD8 T cells. CD4 T cell subsets also showed enhanced STAT1 phosphorylation in response to exogenous IL-7.

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“…HIV-mediated depletion of CD4 + T cells is a direct consequence of both productive virus infection [18] and induction of Fas-mediated apoptosis in both HIV-infected and -uninfected cells [19]. In addition to these direct mechanisms of HIV-induced T cell depletion, increasing evidence has implicated chronic activation of plasmacytoid DCs as being an indirect mechanism of T cell dysfunction and cytotoxicity [20,21]. In this setting, pulmonary plasmacytoid DCs interact with HIV via CD4,resulting in internalization of the virus.…”

mentioning

confidence: 99%

“…In this setting, pulmonary plasmacytoid DCs interact with HIV via CD4,resulting in internalization of the virus. In the cell cytoplasm, viral RNA is recognized by intracellular pathogen recognition receptors known as Toll-like receptors (TLRs)-7 and -9 [20][21][22][23], and possibly by the more recently described cytoplasmic pathogen nucleic acid sensors [24]. This leads, in turn, to excessive and sustained production of: i) type I interferon (IFN); ii) the tryptophan catabolizing enzyme, indoleamine 2,3-dioxygenase; and iii) the cytokine, transforming growth factor β (TGF-β), all of which contribute to immune dysfunction [20,[25][26][27][28][29][30][31][32][33].…”

mentioning

confidence: 99%