CCL2: a Chemokine Potentially Promoting Early Seeding of the Latent HIV Reservoir

Packard, Thomas; Schwarzer, Roland; Herzig, Eytan; Rao, Deepashri; Luo, Xiaoyu; Egedal, Johanne H; Hsiao, Feng; Widera, Marek; Hultquist, Judd F.; Grimmett, Zachary W.; Messer, Ronald J.; Krogan, Nevan J.; Deeks, Steven G.; Roan, Nadia R.; Dittmer, Ulf; Hasenkrug, Kim J.; Greene, Warner C.

doi:10.1128/mbio.01891-22

Cited by 12 publications

(13 citation statements)

References 63 publications

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“…The deleterious effects of chronic upregulation of IL-32 and IL-32-mediated chemokine expression may also expand beyond atherosclerosis. For instance, CCL-2 was recently shown to mediate early seeding of the HIV reservoir by recruiting a unique subset of CCR2/5+ CD4+ T-cells which become infected and form a significant reservoir for latent infection [ 58 ]. Similar studies were also reported on CXCL-1 (an IL-32 induced chemokine) on the enhancement of HIV replication [ 59 ].…”

Section: Discussionmentioning

confidence: 99%

Differential Impact of IL-32 Isoforms on the Functions of Coronary Artery Endothelial Cells: A Potential Link with Arterial Stiffness and Atherosclerosis

Bunet

Cardinal

Ramani

et al. 2023

Viruses

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Chronic inflammation is associated with higher risk of cardiovascular disease (CVD) in people living with HIV (PLWH). We have previously shown that interleukin-32 (IL-32), a multi-isoform proinflammatory cytokine, is chronically upregulated in PLWH and is linked with CVD. However, the mechanistic role of the different IL-32 isoforms in CVD are yet to be identified. In this study, we aimed to investigate the potential impact of IL-32 isoforms on coronary artery endothelial cells (CAEC), whose dysfunction represents a major factor for atherosclerosis. Our results demonstrated that the predominantly expressed IL-32 isoforms (IL-32β and IL-32γ) have a selective impact on the production of the proinflammatory cytokine IL-6 by CAEC. Furthermore, these two isoforms induced endothelial cell dysfunction by upregulating the expression of the adhesion molecules ICAM-I and VCAM-I and the chemoattractants CCL-2, CXCL-8 and CXCL-1. IL-32-mediated expression of these chemokines was sufficient to drive monocyte transmigration in vitro. Finally, we demonstrate that IL-32 expression in both PLWH and controls correlates with the carotid artery stiffness, measured by the cumulated lateral translation. These results suggest a role for IL-32-mediated endothelial cell dysfunction in dysregulation of the blood vessel wall and that IL-32 may represent a therapeutic target to prevent CVD in PLWH.

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Section: Discussionmentioning

confidence: 99%

Differential Impact of IL-32 Isoforms on the Functions of Coronary Artery Endothelial Cells: A Potential Link with Arterial Stiffness and Atherosclerosis

Bunet

Cardinal

Ramani

et al. 2023

Viruses

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“…One marker, CCL2, correlated to HIV infection and was elevated in HIV‐positive PwH. CCL2 is a prominent cytokine produced after HIV infection and also promotes the viral persistence 36 . And CCL2 plays also a dominant role in the development of osteoarthritis pain 37 .…”

Section: Discussionmentioning

confidence: 99%

“…CCL2 is a prominent cytokine produced after HIV infection and also promotes the viral persistence. 36 And CCL2 plays also a dominant role in the development of osteoarthritis pain. 37 As CCL2 was not elevated in HIV-negative PwH, CCL2 is obviously a more relevant marker for HIV infection than for (other) inflammation in PwH.…”

Section: Marker ß-Ngf Pwh ß-Ngf Conmentioning

confidence: 99%

Neuroinflammatory markers in patients with haemophilia and healthy controls: Where are the differences?

Wehmeier,

Orth,

Höppe

et al. 2023

Haemophilia

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IntroductionPeople with haemophilia (PwH) suffer from haemophilic arthropathy which is accompanied by acute and chronic inflammation. The aim of this study was to examine the neuroinflammatory network operative in PwH and to compare it to healthy controls.Material and MethodsBlood samples were collected from 41 PwH (age 54.7 ± 11.7 years) and 33 healthy controls (age 50.9 ± 10.5 years) and the levels of 13 neuroinflammatory markers were analyzed by applying an antibody‐based detection kit in a flow cytometer.ResultsFrom 13 analyzed markers, three—ß‐nerve growth factor (ß‐NGF), soluble receptor for advanced glycation endproducts (sRAGE) and Interleukin‐18 (IL‐18) differed significantly between the groups (ß‐NGF p = .045; sRAGE p = .003; IL‐18 p = .007). While ß‐NGF was downregulated in PwH, sRAGE and IL‐18 were upregulated. None of the analyzed markers corelated to the joint status of PwH while CCL2 (C‐C motif ligand 2 chemokine) correlated to HIV infections in PwH (r = .313, p = .007). Correlation analyses of the markers studied also revealed many differences between PwH and controls suggesting a number of deregulations in PwH.ConclusionThe altered levels of sRAGE and ß‐NGF in PwH, which have not been analyzed in PwH before, may help to understand the neuroinflammatory network operative in PwH. The general inflammatory processes in PwH and the involved biomarkers in PwH remain poorly understood. PwH could benefit from new therapies against neuroinflammation which may help to reduce inflammation or also chronic pain.

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“…1). CD4 + T cells from LT have been shown to rapidly produce CCL2 as an innate immune response during early stages of HIV infection, attracting infected CCR2/CCR5 + CD4 + central memory T cells (T CM ) towards the tissue, likely expanding the reservoir [11]. However, the impact of ART and acute infection resolution on long-term memory persistence in the body remains largely undefined.…”

Section: Tissue-reservoir Establishmentmentioning

confidence: 99%

Targeting HIV persistence in the tissue

Pieren,

Benítez-Martínez,

Genescà

2024

Current Opinion in HIV and AIDS

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Purpose of review The complex nature and distribution of the HIV reservoir in tissue of people with HIV remains one of the major obstacles to achieve the elimination of HIV persistence. Challenges include the tissue-specific states of latency and viral persistence, which translates into high levels of reservoir heterogeneity. Moreover, the best strategies to reach and eliminate these reservoirs may differ based on the intrinsic characteristics of the cellular and anatomical reservoir to reach. Recent findings While major focus has been undertaken for lymphoid tissues and follicular T helper cells, evidence of viral persistence in HIV and non-HIV antigen-specific CD4+ T cells and macrophages resident in multiple tissues providing long-term protection presents new challenges in the quest for an HIV cure. Considering the microenvironments where these cellular reservoirs persist opens new venues for the delivery of drugs and immunotherapies to target these niches. New tools, such as single-cell RNA sequencing, CRISPR screenings, mRNA technology or tissue organoids are quickly developing and providing detailed information about the complex nature of the tissue reservoirs. Summary Targeting persistence in tissue reservoirs represents a complex but essential step towards achieving HIV cure. Combinatorial strategies, particularly during the early phases of infection to impact initial reservoirs, capable of reaching and reactivating multiple long-lived reservoirs in the body may lead the path.

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CCL2: a Chemokine Potentially Promoting Early Seeding of the Latent HIV Reservoir

Abstract: There are currently over 35 million people living with HIV worldwide, and we still have no vaccine or scalable cure. One of the difficulties with HIV is its ability to rapidly establish a viral reservoir in lymphoid tissues that allows it to elude antivirals and the immune system.

Cited by 12 publications

References 63 publications

Differential Impact of IL-32 Isoforms on the Functions of Coronary Artery Endothelial Cells: A Potential Link with Arterial Stiffness and Atherosclerosis

Differential Impact of IL-32 Isoforms on the Functions of Coronary Artery Endothelial Cells: A Potential Link with Arterial Stiffness and Atherosclerosis

Neuroinflammatory markers in patients with haemophilia and healthy controls: Where are the differences?

Targeting HIV persistence in the tissue

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