Faculty Opinions recommendation of Evidence of dysregulation of dendritic cells in primary HIV infection.

Plasmacytoid dendritic cells (pDCs) are innate immune cells able to produce large quantities of type I interferons (IFN) when activated. Human immunodeficiency virus (HIV)-infected patients show generalized immune dysfunction characterized in part by chronic interferon response. In this study we investigated the role of dendritic cells inactivating and maintaining this response. Specifically we compared the IFN geneactivity in pDCs in response to several viruses and TLR agonists. We hypothesized that 1) the pattern of IFN gene transcription would differ in pDCs treated with HIV than with other agents, and 2) that pDCs from patients from different stages of disease would respond differently to the stimulations. To test these hypotheses, we obtained pDCs from 15 HIV-infected and uninfected individuals and treated freshly isolated pDCs with either HIV (BAL strain), influenza virus (A/PR/8/34), Sendai virus (Cantell strain), TLR7 agonist(imiquimod), or TLR9 agonist (CpG-ODN) for 6h. Type I IFN gene transcription was monitored by real time qPCRfor IFNA1, A2, A5, A6, A8,A17, B1, and E1, and cytokine levels were assayed by Cytometric Bead Arrays forTNF?, IL6, IL8, IL10, IL1?, and IL12p70. pDC function as determined by these two assays showed no difference between HIV-infected and uninfected patients or between patients with early or chronic infection. Specifically, HIV did notinduce type I IFN gene expression, whereas influenza virus, Sendai virus and imiquimod did. Similarly, HIV failed to induce any cytokine release from pDCs in contrast to influenza virus, Sendai virus and imiquimod, which stimulatedrelease of TNF?, IL6, or IL8. Together these results suggest that the reaction of pDCs to HIV virus is quantitatively different from the response to agents such as virus, Sendai virus, and imiquimod. In addition, pDCs from HIV-infected persons have responses similar to pDCs from uninfected donors, suggesting, that the DC function may not be affected by HIV infection.

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A mature NK profile is associated with virologic control in primary HIV infection

10.26226/morressier.56d6be6fd462b80296c96dc3 ◽

2016 ◽

Author(s):

Antoine Chéret

Keyword(s):

Hiv Infection ◽

Primary Hiv Infection ◽

Virologic Control

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Faculty Opinions recommendation of IL-10 induces aberrant deletion of dendritic cells by natural killer cells in the context of HIV infection.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.3485958.3180056 ◽

2010 ◽

Author(s):

Yufei Wang

Keyword(s):

Dendritic Cells ◽

Natural Killer Cells ◽

Hiv Infection ◽

Natural Killer ◽

Killer Cells

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Impact of Delaying Antiretroviral Treatment during Primary HIV Infection on Telomere Length

The Journal of Infectious Diseases ◽

10.1093/infdis/jiab186 ◽

2021 ◽

Author(s):

Marieke Raffenberg ◽

Tanja Engel ◽

Isabella C Schoepf ◽

Neeltje A Kootstra ◽

Peter Reiss ◽

...

Keyword(s):

Hiv Infection ◽

Telomere Length ◽

Antiretroviral Treatment ◽

Mononuclear Cells ◽

Multivariable Analysis ◽

Limited Effect ◽

Peripheral Blood Mononuclear ◽

Primary Hiv Infection ◽

Hiv Seroconversion ◽

Chronic Hiv Infection

Abstract Background Telomere length (TL) shortens during aging, HIV-seroconversion and untreated chronic HIV infection. It is unknown whether early antiretroviral therapy (ART) start is associated with less TL shortening during primary HIV infection (PHI). Methods We measured TL in peripheral blood mononuclear cells by quantitative PCR in participants of the Zurich PHI Study with samples available for >6 years. We obtained uni-/multivariable estimates from mixed-effects models and evaluated the association of delaying ART start or interrupting ART with baseline and longitudinal TL. Results In 105 participants with PHI (median age 36 years, 9% women), median ART delay was 25, 42, and 60 days, respectively, in the 1 st (shortest), 2 nd, and 3 rd (longest) ART delay tertile. First ART delay tertile was associated with longer baseline TL (p for trend=0.034), and longer TL over 6 years, but only with continuous ART (p<0.001), not if ART was interrupted >12 months (p=0.408). In multivariable analysis, participants in the 2 nd and 3 rd ART delay tertile had 17.6% (5.4-29.7%; p=0.004) and 21.5% (9.4-33.5%; p<0.001) shorter TL, after adjustment for age, with limited effect modification by clinical variables. Discussion In PHI, delaying ART start for even a matter of weeks was associated with significant and sustained TL shortening.

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