Role of interleukin-4 and monocyte chemoattractant protein-1 in the neuropathogenesis of X4 simian human immunodeficiency virus infection in macaques

Mancuso, Roberta; Mazziotti, Romina; Valli, Maria Beatrice; Borghi, Elisa; Delbue, Serena; Saresella, Marina; Marventano, Ivana; Rusconi, Elena; Marzorati, M.; Cazzullo, A. Guareschi; Ferrante, Pasquale

doi:10.1080/13550280490270798

Cited by 4 publications

(4 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was previously shown that IL-4, favoring M2 macrophage polarization, directly activates tissue-resident macrophages to proliferate in vivo 841. Very interestingly, IL-4 was also previously shown as a biomarker for simian-human immunodeficiency virus encephalitis42434445. It is thus possible that IL-4-driven neuroinflammation is responsible for proliferation of perivascular macrophages.…”

Section: Discussionmentioning

confidence: 95%

Proliferation of Perivascular Macrophages Contributes to the Development of Encephalitic Lesions in HIV-Infected Humans and in SIV-Infected Macaques

Filipowicz

McGary

Holder

et al. 2016

Sci Rep

View full text Add to dashboard Cite

The aim of the present study was to investigate if macrophage proliferation occurs in the brain during simian immunodeficiency virus (SIV) infection of adult macaques. We examined the expression of the Ki-67 proliferation marker in the brains of uninfected and SIV-infected macaques with or without encephalitis. Double-label immunohistochemistry using antibodies against the pan-macrophage marker CD68 and Ki-67 showed that there was a significant increase in CD68+Ki-67+ cells in macaques with SIV encephalitis (SIVE) compared to uninfected and SIV-infected animals without encephalitis, a trend that was also confirmed in brain samples from patients with HIV encephalitis. Multi-label immunofluorescence for CD163 and Ki-67 confirmed that the vast majority of Ki-67+ nuclei were localized to CD163+ macrophages in perivascular cuffs and lesions. The proliferative capacity of Ki-67+ perivascular macrophages (PVM) was confirmed by their nuclear incorporation of bromodeoxyuridine. Examining SIVE lesions, using double-label immunofluorescence with antibodies against SIV-Gag-p28 and Ki-67, showed that the population of Ki-67+ cells were productively infected and expanded proportionally with lesions. Altogether, this study shows that there are subpopulations of resident PVM that express Ki-67 and are SIV-infected, suggesting a mechanism of macrophage accumulation in the brain via PVM proliferation.

show abstract

Section: Discussionmentioning

confidence: 95%

Proliferation of Perivascular Macrophages Contributes to the Development of Encephalitic Lesions in HIV-Infected Humans and in SIV-Infected Macaques

Filipowicz

McGary

Holder

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…CCL2 has been found in cerebrospinal fluid of infected patients (Cinque et al, 1998;Sanders et al, 1998) as well as of simian immunodeficiency virus-infected macaques (Buch et al, 2004;Zink et al, 2001). It has been identified as the elective chemoattractant factor among other chemokines for the transmigration of HIV-1infected leukocytes across the BBB (Eugenin et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Astrocytes contacting HIV‐1‐infected macrophages increase the release of CCL2 in response to the HIV‐1‐dependent enhancement of membrane‐associated TNFα in macrophages

Muratori

Mangino

Affabris

et al. 2010

Glia

View full text Add to dashboard Cite

The presence of human immunodeficiency virus (HIV)-infected macrophages in the parenchyma of central nervous system is an hallmark of acquired immunodeficiency syndrome-related neuroinflammation. Once penetrated the blood-brain barrier (BBB), macrophages closely interact with astrocytes, beginning with those lying beneath the BBB endothelium. By investigating the consequences of the cell-cell interaction between HIV-infected macrophages and astrocytes, we observed that the HIV-1 expression in macrophagic cells correlated with increased chemotactic activity in supernatants of astroglial cells. Gene array analysis revealed an impressive increase in the transcription of the gene for the CCL2/MCP-1 chemokine in astroglial cells isolated from HIV-1-infected co-cultures compared with cells from uninfected co-cultures. This phenomenon coupled with the increase in CCL2 release and depended on the cell-cell contact. In addition, it was a consequence of the HIV-1-induced enhancement of membrane-associated tumor necrosis factor-α in macrophagic cells, and correlated with increased levels of nuclear factor kappaB activation in astroglial cells. These observations could mirror a mechanism of recruitment of leukocytes through the BBB, likely contributing to the increase in both viral load and inflammation in central nervous system of HIV-infected patients.

show abstract

“…However, baboons infected with either SHIV KU or SHIV 89.6P demonstrated productive infection of microglia (Kanmogne et al , 2002). Another study has demonstrated that the presence of IL-4 is necessary for the induction of neuropathology in X4-tropic strains of SHIV (Buch et al , 2004b). …”

Section: Shiv Infection In Macaquesmentioning

confidence: 99%

Nonhuman primate models of NeuroAIDS

et al. 2008

Self Cite

View full text Add to dashboard Cite

Human Immunodeficiency virus (HIV), the virus that causes acquired immunodeficiency syndrome (AIDS), also manifests neurological complications. HIV-associated dementia (HAD) is the most severe form of HIV-induced neurocognitive disorders. HIV encephalitis (HIVE), the pathological correlate of HAD, is characterized by the formation of multinucleated giant cells and microglial nodules, astrocytosis, and neuronal damage and loss. Pathological evaluation of HAD disease progression in humans is not possible, with the only data collected being from individuals who have succumbed to the disorder, a snap shot of end-stage disease at best. Therefore, pertinent animal models have been developed to alleviate this gap of knowledge in the field of neurovirology and neuroinflammation. In general, the most widely used animal models are the simian immunodeficiency virus (SIV) and the chimeric simian/human immunodeficiency virus (SHIV) macaque model systems. Although both SIV and SHIV model systems are able to potentiate neuroinvasion and the concomitant neuropathology similar to that seen in the human syndromes, the innate differences between the two in disease pathogenesis and progression make for two separate, yet effective, systems for the study of HIV-associated neuropathology.

show abstract

Role of interleukin-4 and monocyte chemoattractant protein-1 in the neuropathogenesis of X4 simian human immunodeficiency virus infection in macaques

Cited by 4 publications

References 18 publications

Proliferation of Perivascular Macrophages Contributes to the Development of Encephalitic Lesions in HIV-Infected Humans and in SIV-Infected Macaques

Proliferation of Perivascular Macrophages Contributes to the Development of Encephalitic Lesions in HIV-Infected Humans and in SIV-Infected Macaques

Astrocytes contacting HIV‐1‐infected macrophages increase the release of CCL2 in response to the HIV‐1‐dependent enhancement of membrane‐associated TNFα in macrophages

Nonhuman primate models of NeuroAIDS

Contact Info

Product

Resources

About