Human Immunodeficiency Virus Type 1 Infection Modulates the Interleukin (IL)–1β and IL‐6 Responses of Human Macrophages to CD40 Ligand Stimulation

Bergamini, Alberto; Bolacchi, Francesca; Bongiovanni, Barbara; Colizzi, Vittorio; Cappelli, Giulia; Uccella, Ilaria; Cepparulo, Mario; Capozzi, M.; Mancino, Giorgio; Rocchi, G

doi:10.1086/315803

Cited by 10 publications

(6 citation statements)

References 53 publications

(55 reference statements)

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“…In addition, whole-blood transcriptomic profiling demonstrated a short-term delay of viremia, with macrophage-mediated proinflammatory responses as the important hallmark, independently of the vaccine regimen. Macrophage activation and its proinflammatory consequences are associated with efficient viral replication in acute HIV/SIV infection in vivo (42)(43)(44). On the other hand, early establishment of an anti-inflammatory milieu is predictive of disease nonprogression in the case of natural hosts (45).…”

Section: Discussionmentioning

confidence: 99%

Multiple Low-Dose Challenges in a Rhesus Macaque AIDS Vaccine Trial Result in an Evolving Host Response That Affects Protective Outcome

Selinger

Štrbo

Gonzalez

et al. 2014

Clin. Vaccine Immunol.

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dUsing whole-blood transcriptional profiling, we investigated differences in the host response to vaccination and challenge in a rhesus macaque AIDS vaccine trial. Samples were collected from animals prior to and after vaccination with live, irradiated vaccine cells secreting the modified endoplasmic reticulum chaperone gp96-Ig loaded with simian immunodeficiency virus (SIV) peptides, either alone or in combination with a SIV-gp120 protein boost. Additional samples were collected following multiple low-dose rectal challenges with SIV mac251 . Animals in the boosted group had a 73% reduced risk of infection. Surprisingly, few changes in gene expression were observed during the vaccination phase. Focusing on postchallenge comparisons, in particular for protected animals, we identified a host response signature of protection comprised of strong interferon signaling after the first challenge, which then largely abated after further challenges. We also identified a host response signature, comprised of early macrophage-mediated inflammatory responses, in animals with undetectable viral loads 5 days after the first challenge but with unusually high viral titers after subsequent challenges. Statistical analysis showed that prime-boost vaccination significantly lowered the probability of infection in a time-consistent manner throughout several challenges. Given that humoral responses in the prime-boost group were highly significant prechallenge correlates of protection, the strong innate signaling after the first challenge suggests that interferon signaling may enhance vaccine-induced antibody responses and is an important contributor to protection from infection during repeated low-dose exposure to SIV.

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Section: Discussionmentioning

confidence: 99%

Multiple Low-Dose Challenges in a Rhesus Macaque AIDS Vaccine Trial Result in an Evolving Host Response That Affects Protective Outcome

Selinger

Štrbo

Gonzalez

et al. 2014

Clin. Vaccine Immunol.

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“…The concentrations of TNFα, IL‐6 , and eventually IL‐1β in plasma, in cerebrospinal fluid and in the lymph nodes , are elevated. Peripheral blood mononuclear cells (PBMCs) from HIV‐1‐infected individuals usually overproduce inflammatory cytokines spontaneously or under stimulation . Of note, various groups have reported that the expression of inflammatory cytokine mRNAs in PBMCs and/or the plasma level of inflammatory cytokines is not normalized under HAART , or not even decreased .…”

Section: Immune Activation In Hiv‐1 Infection: a Global Phenomenonmentioning

confidence: 99%

Immune activation in the course of HIV‐1 infection: Causes, phenotypes and persistence under therapy

et al. 2015

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Systemic immune activation is a striking consequence of HIV-1 infection. Even in virologically suppressed patients, some hyperactivity of the immune system and even of the endothelium and of the coagulation pathway may persist. Apart from immune deficiency, this chronic activation may contribute to various morbidities including atherothrombosis, neurocognitive disorders, liver steatosis and osteoporosis, which are currently main challenges. It is therefore of major importance to better understand the causes and the phenotypes of immune activation in the course of HIV-1 infection. In this review we will discuss the various causes of immune activation in HIV-1 infected organisms: the presence of the virus together with other microbes, eventually coming from the gut, CD4+ T cell lymphopenia, senescence and dysregulation of the immune system, and/or genetic factors. We will also describe the activation of the immune system: CD4+ and CD8+ T cells, B cells, NKT and NK cells, dendritic cells, monocytes and macrophages, and neutrophils of the inflammation cascade, as well as of the endothelium and the coagulation system. Finally, we will see that antiretroviral therapy reduces the hyperactivity of the immune and coagulation systems and the endothelial dysfunction, but often does not abolish it. A better knowledge of this phenomenon might help us to identify biomarkers predictive of non AIDS-linked comorbidities, and to define new strategies aiming at preventing their emergence.

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“…HIV infection results in increased numbers of activated circulating B cells producing non-specific IgG [20] likely driven by an altered cytokine milieu [21]. High immunoglobulin concentrations are found in the lung of HIV-infected subjects [22,23].…”

Section: Effect Of Hiv On Pulmonary Immune Responsesmentioning

confidence: 99%

HIV-related lung disorders

Twigg

Knox

2007

Drug Discovery Today: Disease Mechanisms

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Highly active antiretroviral therapy (HAART) has dramatically altered the spectrum of morbidity and mortality in HIV-infected patients. This has been attributed to improvements in the lung microenvironment leading to enhanced pulmonary immunity, either by preventing the progressive loss of immune function or by actually promoting immune restoration. However, these changes have been accompanied by the recognition of new pulmonary complications in HIV-infected subjects, especially those associated with immune reconstitution. In this review we will describe how HIV infection alters the normal pulmonary environment, highlight the effect of HAART on these perturbations, and discuss potential complications of HAART in the lung, focusing on the pulmonary immune reconstitution inflammatory syndrome.

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Human Immunodeficiency Virus Type 1 Infection Modulates the Interleukin (IL)–1β and IL‐6 Responses of Human Macrophages to CD40 Ligand Stimulation

Cited by 10 publications

References 53 publications

Multiple Low-Dose Challenges in a Rhesus Macaque AIDS Vaccine Trial Result in an Evolving Host Response That Affects Protective Outcome

Multiple Low-Dose Challenges in a Rhesus Macaque AIDS Vaccine Trial Result in an Evolving Host Response That Affects Protective Outcome

Immune activation in the course of HIV‐1 infection: Causes, phenotypes and persistence under therapy

HIV-related lung disorders

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