Brief Report: Soluble CD163 in CMV-Infected and CMV-Uninfected Subjects on Virologically Suppressive Antiretroviral Therapy in the ICONA Cohort

Vita, Serena; Lichtner, Miriam; Marchetti, Giulia; Mascia, Claudia; Merlini, Esther; Cicconi, Paola; Vullo, Vincenzo; Viale, Pierluigi; Costantini, Andrea; Monforte, Antonella d’Arminio

doi:10.1097/qai.0000000000001232

Cited by 16 publications

(8 citation statements)

References 48 publications

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“…Differences in the composition of the gut microbiome, for example, caused by specific sexual practices or frequent antibiotic use could hypothetically contribute to the lower CD4/CD8 ratios we observed in MSM. Contrary to our findings, previous studies, but conducted only in HIV-positive persons, have reported higher sCD14, sCD163, hs-CRP, and IL-6 levels associated with a lower CD4/CD8 ratio [ 4 , 35 ]. Specifically, Serrano-Villar et al [ 4 ] reported such associations related only to lower CD4 counts, but not higher CD8 counts, and to be absent in HIV-positive participants with >500 CD4 cells/mm 3 .…”

Section: Discussioncontrasting

confidence: 99%

Human Immunodeficiency Virus (HIV)-Negative Men Who Have Sex With Men Have Higher CD8+ T-Cell Counts and Lower CD4+/CD8+ T-Cell Ratios Compared With HIV-Negative Heterosexual Men

Verboeket

Wit

Verheij

et al. 2020

The Journal of Infectious Diseases

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Background We previously reported T-cell senescence to be similar in people with human immunodeficiency virus (PWH) with suppressed viremia (predominantly men who have sex with men [MSM]) and human immunodeficiency virus (HIV)-negative otherwise comparable controls but greater than in healthy blood donors. This led us to compare CD4+ and CD8+ T-cell counts and CD4+/CD8+ ratios between HIV-negative MSM and men who only have sex with women (MSW) and relate observed differences in behavioral factors and infectious exposures, including cytomegalovirus (CMV) infection. Methods In 368 HIV-negative MSM and 72 HIV-negative MSW, T lymphocyte phenotyping was performed 3 times biennially. Baseline CMV serology and sexually transmitted infection (STI) incidence and/or STI seroprevalence, sexual, and substance-use behavior data were collected during study visits. Results Men who have sex with men, compared with MSW, had higher CD8+ counts (551 vs 437 cells/mm3, P < .001), similar CD4+ counts (864 vs 880 cells/mm3, P = .5), and lower CD4+/CD8+ ratios (1.84 vs 2.47, P < .001). Differences were most pronounced for MSM with >10 recent sex partners and partly explained by higher CMV seroprevalence in MSM. Conclusions These findings suggest that factors other than HIV may, in both PWH and certain HIV-negative MSM, contribute to a low CD4+/CD8+ ratio. Whether this, like in PWH, contributes to comorbidity risk in HIV-negative MSM requires further study.

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Section: Discussioncontrasting

confidence: 99%

Human Immunodeficiency Virus (HIV)-Negative Men Who Have Sex With Men Have Higher CD8+ T-Cell Counts and Lower CD4+/CD8+ T-Cell Ratios Compared With HIV-Negative Heterosexual Men

Verboeket

Wit

Verheij

et al. 2020

The Journal of Infectious Diseases

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“…In PLWHIV on cART, an association between increased CMV IgG responses and systemic inflammation, defined by increased levels of CRP, CD163, and IL-6 in serum, has previously been reported 20 , 21 , 41 , 42 , and an association between CMV-seropositivity and IL-6 levels has also been found in healthy adults 43 . However, no previous studies have addressed whether this relationship also applies to CMV-specific T-cell responses.…”

Section: Discussionmentioning

confidence: 78%

Cytomegalovirus-specific T-cells are associated with immune senescence, but not with systemic inflammation, in people living with HIV

Ballegaard

Braendstrup

Pedersen

et al. 2018

Sci Rep

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In people living with HIV (PLWHIV), coinfection with cytomegalovirus (CMV) has been associated with inflammation, immunological ageing, and increased risk of severe non-AIDS related comorbidity. The effect of CMV-specific immune responses on systemic inflammation, immune activation and T-cell senescence was evaluated in 53 PLWHIV treated with combination antiretroviral therapy (cART). Activated-, terminally differentiated-, naïve-, and senescent T-cells were assessed by flow cytometry, and plasma levels of CMV IgG, interleukin-6, tumor necrosis factor-α, high-sensitivity C-reactive protein and soluble-CD14 were measured. In PLWHIV, expression of interleukin-2, tumor necrosis factor-α and interferon-γ was measured by intracellular-cytokine-staining after stimulation of T-cells with CMV-pp65, CMV-IE1, and CMV-gB. Increased CMV-specific T-cell responses were associated with a higher ratio of terminally differentiated/naïve CD8+ T-cells and with increased proportions of senescent CD8+ T-cells, but not with systemic inflammation or sCD14. Increased CMV-specific CD4+ T-cell responses were associated with increased proportions of activated CD8+ T-cells. In PLWHIV with expansion of CMV-specific T-cells or increased T-cell senescence, CMV-specific polyfunctionality was maintained. That the magnitude of the CMV-specific T-cell response was associated with a senescent immune phenotype, suggests that a dysregulated immune response against CMV may contribute to the immunological ageing often described in PLWHIV despite stable cART.

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“…The frequency of CD16+CD163+ monocytes is positively correlated with the viral load. Of note, the CMV status is associated with increased levels of soluble CD163 in the plasma of HIV-infected individuals treated with ART [ 135 ]. The frequency of intermediate monocytes positively correlated with levels of the inflammation marker IL-6, the monocyte activation marker soluble CD14 (sCD14) and the cardiovascular disease marker high-sensitivity C-reactive protein (hs-CRP) [ 136 ].…”

Section: Monocytes and Hivmentioning

confidence: 99%

The Biology of Monocytes and Dendritic Cells: Contribution to HIV Pathogenesis

Wacleche

Tremblay

Routy

et al. 2018

Viruses

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Myeloid cells such as monocytes, dendritic cells (DC) and macrophages (MΦ) are key components of the innate immune system contributing to the maintenance of tissue homeostasis and the development/resolution of immune responses to pathogens. Monocytes and DC, circulating in the blood or infiltrating various lymphoid and non-lymphoid tissues, are derived from distinct bone marrow precursors and are typically short lived. Conversely, recent studies revealed that subsets of tissue resident MΦ are long-lived as they originate from embryonic/fetal precursors that have the ability to self-renew during the life of an individual. Pathogens such as the human immunodeficiency virus type 1 (HIV-1) highjack the functions of myeloid cells for viral replication (e.g., MΦ) or distal dissemination and cell-to-cell transmission (e.g., DC). Although the long-term persistence of HIV reservoirs in CD4+ T-cells during viral suppressive antiretroviral therapy (ART) is well documented, the ability of myeloid cells to harbor replication competent viral reservoirs is still a matter of debate. This review summarizes the current knowledge on the biology of monocytes and DC during homeostasis and in the context of HIV-1 infection and highlights the importance of future studies on long-lived resident MΦ to HIV persistence in ART-treated patients.

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Brief Report: Soluble CD163 in CMV-Infected and CMV-Uninfected Subjects on Virologically Suppressive Antiretroviral Therapy in the ICONA Cohort

Abstract: CMV coinfection could be a major driver of monocyte/macrophage activation in virally suppressed HIV+ individuals and might explain the increased risk of non-AIDS morbidity/mortality in HIV/CMV-coinfected subjects.

Cited by 16 publications

References 48 publications

Human Immunodeficiency Virus (HIV)-Negative Men Who Have Sex With Men Have Higher CD8+ T-Cell Counts and Lower CD4+/CD8+ T-Cell Ratios Compared With HIV-Negative Heterosexual Men

Human Immunodeficiency Virus (HIV)-Negative Men Who Have Sex With Men Have Higher CD8+ T-Cell Counts and Lower CD4+/CD8+ T-Cell Ratios Compared With HIV-Negative Heterosexual Men

Cytomegalovirus-specific T-cells are associated with immune senescence, but not with systemic inflammation, in people living with HIV

The Biology of Monocytes and Dendritic Cells: Contribution to HIV Pathogenesis

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