Changes to alveolar macrophage phenotype in HIV infected individuals with normal CD4 counts and no respiratory disease.

Lipman, Marc; Johnson, Margaret; Bray, D.; Poulter, LW

doi:10.1136/thx.50.7.777

Cited by 8 publications

(4 citation statements)

References 31 publications

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“…The mucosa of the female LGT in HIV1 women exhibits fundamental changes in lymphocyte and macrophage populations and in Ig and cytokine production even in the absence of LGT symptoms. Similar mucosal derangements are seen in the gut [18,30] and lung [31,32] of HIV-infected patients. Unlike the gut and lung, however, which are major sites of opportunistic infection…”

Section: Discussionsupporting

confidence: 48%

Immunity in the Female Lower Genital Tract and the Impact of HIV Infection

Ahmed¹,

Al-Doujaily²,

Johnson

et al. 2001

Scand J Immunol

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This study investigates the distribution of immunocompetent cells in the ectocervix, and cytokine and immunoglobulin (Ig) levels in cervicovaginal secretions to determine whether they are altered in asymptomatic human immunodeficiency virus (HIV) infection. Ectocervical biopsies from 10 HIV1 and 10 presumed HIV-ve women were studied by immunocytochemistry. Levels of Igs in cervicovaginal secretions were quantified by radial immunodiffusion (RID) and cytokine levels by ELISA. HIV1 women had significantly increased numbers of CD8 1 lymphocytes resulting in reversal of the CD4:CD8 ratio. There was a significant increase in the proportion of activated CD81 HLA-DR1 and CD4 1 HLA-DR 1 lymphocytes, but not in CD81 TIA-11 cells. The epithelium of the cervix from HIV1 subjects showed a significant increase in both numbers of macrophages (CD681) and proportions of activated macrophages (CD681 HLA-DR1) compared to normal. The stroma contained increased proportions of inductive (D11) and suppressive (D11 D71) macrophages but a decrease in effector phagocyte (D71) proportions and Langerhans' cells. Significantly lower tumour necrosis factor (TNF)-a levels were observed in cervicovaginal secretions from HIV1 subjects. IgG levels were 4 times higher and IgM levels twice higher in cervicovaginal secretions from HIV1 women, compared to results from normal subjects. These results suggest a response within the CD8 1 cells in HIV1 women, yet these cells may have a low cytolytic capacity. The raised proportions of HLA-DR1 and D11 CD4 1 macrophages could act as antigen-presenting cells (APC) for CD4 1 CD45RO1 lymphocytes, and represent a local acquired response. However, the close juxtaposition of these cells offers the potential for them to act as a local reservoir of virus and promote its proliferation. The increase of IgG over sIgA in secretions of HIV1 subjects provides evidence suggesting a dysregulation of local humoral immunity.

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Section: Discussionsupporting

confidence: 48%

Immunity in the Female Lower Genital Tract and the Impact of HIV Infection

Ahmed¹,

Al-Doujaily²,

Johnson

et al. 2001

Scand J Immunol

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“…In the alveolar space, the AM is the first line of lung immune defense. HIV impairs AM immune functions [7][8][9][10][11] through dysregulated activation, [13][14][15][16] impaired oxidative burst, 15 and enhanced anti-inflammatory cytokine secretion. 13 In an experimental model using HIV transgenic rats, AM phagocytosis was significantly decreased in HIVinfected rats, compared with phagocytosis in AMs from wildtype rats.…”

Section: Discussionmentioning

confidence: 99%

“…[7][8][9][10][11] In fact, we have previously shown that the AM harbors HIV, even in otherwise healthy subjects with undetectable plasma viral loads, suggesting that the AM is a potential reservoir for the virus. 12 HIV infection also causes derangements in multiple steps of an immune response, including abnormal activation, [13][14][15][16] diminished oxidative burst, 15 increased anti-inflammatory cytokine secretion, 13 and impaired phagocytic capacity. 8,9,12 Most notably, in our previous prospective cross-sectional study of healthy HIV-infected subjects with systemic viral suppression and on ART, AMs from HIV-infected subjects exhibited impaired phagocytic index compared with control subjects.…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of Alveolar Macrophage PPARγ, NADPH Oxidases, and TGFβ₁in Otherwise Healthy HIV-Infected Individuals

Yeligar

Ward

Harris

et al. 2017

AIDS Research and Human Retroviruses

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Despite antiretroviral therapy (ART), respiratory infections increase mortality in individuals living with chronic human immunodeficiency virus (HIV) infection. In experimental and clinical studies of chronic HIV infection, alveolar macrophages (AMs) exhibit impaired phagocytosis and bacterial clearance. Peroxisome proliferator-activated receptor (PPAR)γ, NADPH oxidase (Nox) isoforms Nox1, Nox2, Nox4, and transforming growth factor-beta 1 (TGFβ) are critical mediators of AM oxidative stress and phagocytic dysfunction. Therefore, we hypothesized that HIV alters AM expression of these targets, resulting in chronic lung oxidative stress and subsequent immune dysfunction. A cross-sectional study of HIV-infected (n = 22) and HIV-uninfected (n = 6) subjects was conducted. Bronchoalveolar lavage (BAL) was performed, and AMs were isolated. Lung HO generation was determined by measuring HO in the BAL fluid. In AMs, PPARγ, Nox1, Nox2, Nox4, and TGFβ mRNA (quantitative real-time polymerase chain reaction) and protein (fluorescent immunomicroscopy) levels were assessed. Compared with HIV-uninfected (control) subjects, HIV-infected subjects were relatively older and the majority were African American; ∼86% were on ART, and their median CD4 count was 445, with a median viral load of 0 log copies/ml. HIV infection was associated with increased HO in the BAL, decreased AM mRNA and protein levels of PPARγ, and increased AM mRNA and protein levels of Nox1, Nox2, Nox4, and TGFβ. PPARγ attenuation and increases in Nox1, Nox2, Nox4, and TGFβ contribute to AM oxidative stress and immune dysfunction in the AMs of otherwise healthy HIV-infected subjects. These findings provide novel insights into the molecular mechanisms by which HIV increases susceptibility to pulmonary infections.

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“…Lipman et al . confirmed these findings – they examined alveolar macrophages of HIV infected patients with no respiratory disease and normal CD4 counts and found an increased expression of HLA‐DR compared to non‐HIV infected controls [46].…”

Section: Mhc‐ii Expression In the Brain And Other Tissues Of Aids Patmentioning

confidence: 84%

Interactions between major histocompatibility complex class II surface expression and HIV: implications for pathogenesis

Kamp¹,

Breij

Nottet

et al. 2001

Eur J Clin Investigation

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Although it has been almost 20 years since the first cases of acquired immunodeficiency syndrome (AIDS) were documented, the pathogenesis is still not completely understood. Interactions between major histocompatibility complex (MHC) Class I and human immunodeficiency virus (HIV), resulting in down-regulation of MHC-I surface expression, have been reported to contribute to pathogenesis by suppressing the host's immune response. Interactions between MHC Class II and HIV have also been described, but it is unclear how these contribute to the pathogenesis. MHC-II surface expression on HIVinfected monocytes and monocytic cell lines has been described to be increased as well as decreased when compared to uninfected control monocytes. HIV-specific mechanisms appear to down-regulate MHC-II expression on blood monocytes during HIV-1 infection, whereas host mechanisms up-regulate MHC-II expression in response to infection of blood monocytes as well as brain macrophages. A balance between these two may determine MHC-II expression levels in individual patients.Altogether, HIV seems to be able to benefit from both low and high levels of MHC-II surface expression. The first results in reduced immune surveillance of the host, allowing the virus to replicate faster; the second increases infectivity of the virus as a result of higher MHC-II density on macrophages and virion particles.

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Changes to alveolar macrophage phenotype in HIV infected individuals with normal CD4 counts and no respiratory disease.

Abstract: (Thorax 1995;50:777-781)

Cited by 8 publications

References 31 publications

Immunity in the Female Lower Genital Tract and the Impact of HIV Infection

Immunity in the Female Lower Genital Tract and the Impact of HIV Infection

Dysregulation of Alveolar Macrophage PPARγ, NADPH Oxidases, and TGFβ₁in Otherwise Healthy HIV-Infected Individuals

Interactions between major histocompatibility complex class II surface expression and HIV: implications for pathogenesis

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Changes to alveolar macrophage phenotype in HIV infected individuals with normal CD4 counts and no respiratory disease.

Abstract: (Thorax 1995;50:777-781)

Cited by 8 publications

References 31 publications

Immunity in the Female Lower Genital Tract and the Impact of HIV Infection

Immunity in the Female Lower Genital Tract and the Impact of HIV Infection

Dysregulation of Alveolar Macrophage PPARγ, NADPH Oxidases, and TGFβ1in Otherwise Healthy HIV-Infected Individuals

Interactions between major histocompatibility complex class II surface expression and HIV: implications for pathogenesis

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Product

Resources

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Dysregulation of Alveolar Macrophage PPARγ, NADPH Oxidases, and TGFβ₁in Otherwise Healthy HIV-Infected Individuals