Preferential HIV Infection of CCR6
            <sup>+</sup>
            Th17 Cells Is Associated with Higher Levels of Virus Receptor Expression and Lack of CCR5 Ligands

Alvarez, Yelina; Tuen, Michael; Shen, Guomiao; Nawaz, Fatima; Arthos, James; Wolff, Martin; Poles, Michael A.; Hioe, Catarina E.

doi:10.1128/jvi.01838-13

Cited by 105 publications

(137 citation statements)

References 48 publications

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“…[38][39][40] A recent study in our laboratory demonstrates that the CCR6 + Th17 cells that express high levels of HIV receptors (CD4, CCR5, and the integrin a 4 b 7 ) but lack anti-HIV CC-chemokines are more susceptible to HIV infection than Th1 cells. 41 Furthermore, once the Th17 cells are lost, HIV control with an antiretroviral drug alone is not sufficient to restore this cell population; rather, a combination of anti-retroviral drugs and IL-1b, IL-6, and IL-23 is needed for full expansion of Th17 cells to the levels seen in uninfected controls. 42 HIV infection also damages the intestinal architecture by inducing apoptosis of enterocytes and eliminating mucosal repair mechanisms mediated by Th17 cells and their cytokines IL-17 and IL-22.…”

Section: Selective Depletion Of Cd4 T Cell Subsetsmentioning

confidence: 99%

“…In addition, inducing CD8 and CD4 T cell populations that produce anti-HIV chemokines (MIP-1a, MIP-1b, RANTES) might provide protection to Th17 cells, given that most Th17 cells do not produce anti-HIV chemokines. 39,41 Nonetheless, a minor subset of IL-17 + cells is capable of producing anti-HIV chemokines 41 and possibly other antiviral factors that confer some level of resistance against HIV. Elicitation and expansion of this population by vaccination may be advantageous; however, the types of immunogens, adjuvants, and delivery systems capable of predominantly eliciting this Th17 subset or other desirable Th subsets are not at all known.…”

Section: Selective Depletion Of Cd4 T Cell Subsetsmentioning

confidence: 99%

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Induction of Intestinal Immunity by Mucosal Vaccines As a Means of Controlling HIV Infection

Poles

Alvarez²,

Hioe³

2014

AIDS Research and Human Retroviruses

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CD4+ T cells in the mucosa of the gastrointestinal (GI) tract are preferentially targeted and depleted by HIV. As such, the induction of an effective anti-HIV immune response in the mucosa of the GI tract-through vaccination-could protect this vulnerable population of cells. Mucosal vaccination provides a promising means of inducing robust humoral and cellular responses in the GI tract. Here we review data from the literature about the effectiveness of various mucosal vaccination routes-oral (intraintestinal/tonsilar/sublingual), intranasal, and intrarectal-with regard to the induction of immune responses mediated by cytotoxic T cells and antibodies in the GI mucosa, as well as protective efficacy in challenge models. We present data from the literature indicating that mucosal routes have the potential to effectively elicit GI mucosal immunity and protect against challenge. Given their capacity for the induction of anti-HIV immune responses in the GI mucosa, we propose that mucosal routes, including the nonconventional sublingual, tonsilar, and intrarectal routes, be considered for the delivery of the next generation HIV vaccines. However, further studies are necessary to determine the ideal vectors and vaccination regimens for these routes of immunization and to validate their efficacy in controlling HIV infection. HIV Epidemics and Treatment HIV infection has resulted in the death of millions since the early 1980s, and has been responsible for significant morbidity and decline in quality of life for millions more. Each year, an estimated 50,000 people are newly infected with the virus in the United States alone, adding to the 34 million currently living with the virus worldwide.

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Section: Selective Depletion Of Cd4 T Cell Subsetsmentioning

confidence: 99%

Section: Selective Depletion Of Cd4 T Cell Subsetsmentioning

confidence: 99%

Induction of Intestinal Immunity by Mucosal Vaccines As a Means of Controlling HIV Infection

Poles

Alvarez²,

Hioe³

2014

AIDS Research and Human Retroviruses

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“…The mechanisms leading to a preferential depletion of Th17 cells have been partially elucidated: several studies have shown that Th17 cells are more permissive than Th1 cells to HIV-1 infection both in vitro and in vivo (29)(30)(31)(32). Although Th1 cells, which express the chemokine receptors CXCR3, CCR5, and CXCR4, have been shown to be relatively resistant to HIV infection in vitro (29), the predominant susceptibility of Th17 cells to some HIV strains has been linked to the expression of the chemokine receptors CCR6, CCR9, CCR5, and of the integrin a 4 b 7 , which are also essential for their homing to the intestinal mucosa (33)(34)(35).…”

mentioning

confidence: 99%

Impairment of CCR6+ and CXCR3+ Th Cell Migration in HIV-1 Infection Is Rescued by Modulating Actin Polymerization

Cecchinato

Bernasconi

Speck

et al. 2017

The Journal of Immunology

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CD4+ T cell repopulation of the gut is rarely achieved in HIV-1–infected individuals who are receiving clinically effective antiretroviral therapy. Alterations in the integrity of the mucosal barrier have been indicated as a cause for chronic immune activation and disease progression. In this study, we present evidence that persistent immune activation causes impairment of lymphocytes to respond to chemotactic stimuli, thus preventing their trafficking from the blood stream to peripheral organs. CCR6+ and CXCR3+ Th cells accumulate in the blood of aviremic HIV-1–infected patients on long-term antiretroviral therapy, and their frequency in the circulation positively correlates to levels of soluble CD14 in plasma, a marker of chronic immune activation. Th cells show an impaired response to chemotactic stimuli both in humans and in the pathogenic model of SIV infection, and this defect is due to hyperactivation of cofilin and inefficient actin polymerization. Taking advantage of a murine model of chronic immune activation, we demonstrate that cytoskeleton remodeling, induced by okadaic acid, restores lymphocyte migration in response to chemokines, both in vitro and in vivo. This study calls for novel pharmacological approaches in those pathological conditions characterized by persistent immune activation and loss of trafficking of T cell subsets to niches that sustain their maturation and activities.

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“…However, there was also increased CD4 and a4b7 (an integrin that is involved in HIV binding) expression, which could confound these findings. In addition, T H 17 cells do not express CCR5 ligands, in contrast to T H 1 cells, which was a factor associated with HIV permissiveness [38]. Others have found that increased CCR5 surface expression could be correlated with the susceptibility of early differentiated IL-17 + CD4 T cells, leading the authors to postulate that this may be a possible mechanism for viral permissiveness [39].…”

Section: Involvement Of Ccr6 In Cellular Hiv Pathogenesis T H 17 Cellsmentioning

confidence: 98%

“…Alvarez et al [38] found that although CCR5 expression remained constant between T H 17 and non-T H 17 (CD4 + CCR6 À ) cells, there was higher expression of CXCR4 in the former, suggesting that HIV may target T H 17 cells through this receptor. However, there was also increased CD4 and a4b7 (an integrin that is involved in HIV binding) expression, which could confound these findings.…”

Section: Involvement Of Ccr6 In Cellular Hiv Pathogenesis T H 17 Cellsmentioning

confidence: 99%

CCR6/CCL20 chemokine axis in human immunodeficiency virus immunity and pathogenesis

Lee

Körner

2017

Journal of General Virology

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Recent studies in human immunodeficiency virus (HIV) have garnered interest for the role of CC chemokine receptor 6 (CCR6) and its known ligands, CC chemokine ligand 20 (CCL20) and human b-defensins, in viral entry, dissemination and antiviral immunity. Several studies have suggested that CCR6 may also act as a weak co-receptor of HIV entry, in addition to the canonical CXC chemokine receptor 4 (CXCR4) and CCR5. However, the pathogenic significance has yet to be demonstrated as the observations for preferential infection of CD4 + CCR6 + over CD4 + CCR6 À T cells appear to be independent of CCR6 expression. This indicates means for preferential infection other than CCR6 co-receptor use. Attention has also turned to the inadvertent role of the CCR6/CCL20 axis in attracting key immune cells, including T H 17 cells and dendritic cells, to sites of infection and propagating the virus to other sites of the body. This review article will summarize the latest evidence that the CCR6/CCL20 chemokine axis is playing an important role in HIV pathogenesis and immunity. Further work with in vivo studies is needed to establish the biological and, hence, therapeutic significance of these findings.

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Preferential HIV Infection of CCR6 ⁺ Th17 Cells Is Associated with Higher Levels of Virus Receptor Expression and Lack of CCR5 Ligands

Cited by 105 publications

References 48 publications

Induction of Intestinal Immunity by Mucosal Vaccines As a Means of Controlling HIV Infection

Induction of Intestinal Immunity by Mucosal Vaccines As a Means of Controlling HIV Infection

Impairment of CCR6+ and CXCR3+ Th Cell Migration in HIV-1 Infection Is Rescued by Modulating Actin Polymerization

CCR6/CCL20 chemokine axis in human immunodeficiency virus immunity and pathogenesis

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Preferential HIV Infection of CCR6 + Th17 Cells Is Associated with Higher Levels of Virus Receptor Expression and Lack of CCR5 Ligands

Cited by 105 publications

References 48 publications

Induction of Intestinal Immunity by Mucosal Vaccines As a Means of Controlling HIV Infection

Induction of Intestinal Immunity by Mucosal Vaccines As a Means of Controlling HIV Infection

Impairment of CCR6+ and CXCR3+ Th Cell Migration in HIV-1 Infection Is Rescued by Modulating Actin Polymerization

CCR6/CCL20 chemokine axis in human immunodeficiency virus immunity and pathogenesis

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Product

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Preferential HIV Infection of CCR6 ⁺ Th17 Cells Is Associated with Higher Levels of Virus Receptor Expression and Lack of CCR5 Ligands