R5 HIV productively infects Langerhans cells, and infection levels are regulated by compound<i>CCR5</i>polymorphisms

Kawamura, Tatsuyoshi; Gulden, Forrest O.; Sugaya, Makoto; McNamara, David T.; Borris, Debra L.; Lederman, Michael M.; Orenstein, Jan M.; Zimmerman, Peter A.; Blauvelt, Andrew

doi:10.1073/pnas.1432450100

Cited by 177 publications

(179 citation statements)

References 50 publications

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“…The mechanism of suppressed migration remains elusive, although it is unlikely to be due to the direct infection of DC. HIV and SIV can infect Langerhans cells (53,54); however, evidence for the significant infection of Langerhans cells during progressive infection is lacking. Moreover, Langerhans cells migrate with normal efficiency from the skin in SIV-infected monkeys at the time of peak virus load, indicating that failed Langerhans cell migration is not simply a function of high virus burden (23).…”

Section: Discussionmentioning

confidence: 99%

Parallel Loss of Myeloid and Plasmacytoid Dendritic Cells from Blood and Lymphoid Tissue in Simian AIDS

Brown

Trichel²,

Barratt‐Boyes

2007

The Journal of Immunology

105

141

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The loss of myeloid (mDC) and plasmacytoid dendritic cells (pDC) from the blood of HIV-infected individuals is associated with progressive disease. It has been proposed that DC loss is due to increased recruitment to lymph nodes, although this has not been directly tested. Similarly as in HIV-infected humans, we found that lineage-negative (Lin−) HLA-DR+CD11c+CD123− mDC and Lin−HLA-DR+CD11c−CD123+ pDC were lost from the blood of SIV-infected rhesus macaques with AIDS. In the peripheral lymph nodes of SIV-naive monkeys the majority of mDC were mature cells derived from skin that expressed high levels of HLA-DR, CD83, costimulatory molecules, and the Langerhans cell marker CD1a, whereas pDC expressed low levels of HLA-DR and CD40 and lacked costimulatory molecules, similar to pDC in blood. Surprisingly, both DC subsets were depleted from peripheral and mesenteric lymph nodes and spleens in monkeys with AIDS, although the activation status of the remaining DC subsets was similar to that of DC in health. In peripheral and mesenteric lymph nodes from animals with AIDS there was an accumulation of Lin−HLA-DRmoderateCD11c−CD123− cells that resembled monocytoid cells but failed to acquire a DC phenotype upon culture, suggesting they were not DC precursors. mDC and pDC from the lymphoid tissues of monkeys with AIDS were prone to spontaneous death in culture, indicating that apoptosis may be a mechanism for their loss in disease. These findings demonstrate that DC are lost from rather than recruited to lymphoid tissue in advanced SIV infection, suggesting that systemic DC depletion plays a direct role in the pathophysiology of AIDS.

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Section: Discussionmentioning

confidence: 99%

Parallel Loss of Myeloid and Plasmacytoid Dendritic Cells from Blood and Lymphoid Tissue in Simian AIDS

Brown

Trichel²,

Barratt‐Boyes

2007

The Journal of Immunology

105

141

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“…Vaginal simian immunodeficiency virus (SIV) infection of Rhesus macaques resulted in infected LC beneath the vaginal epithelium within the first day of infection [22]. Infection of biopsies of human cervical and skin of primate foreskin tissue explants show that LC can be infected [23,24]. Topical infection of human vaginal epithelial explants with HIV strongly suggested that LC and non-activated T-lymphocytes are the major cell types expressing HIV antigen in and emigrating from the explants and that they are often associated during emigration with HIV antigen concentrated at their contact region [21].…”

Section: Lc Interactions With Important Human Viruses Hiv and Lcmentioning

confidence: 99%

Langerhans cells and viral immunity

2008

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Langerhans cells (LC) are a unique dendritic cell subset that are located in mucosal stratified squamous epithelium and skin epidermis. Their location is ideally suited for their function as antigen presenting cells that capture invading viruses and induce anti-viral immunity. However, it is becoming evident that the interaction between LC and viruses can result in different responses, depending on the virus and the receptors involved. Here we will discuss the recent data on the similarities and differences in roles of LC in viral immunity to and infection with HIV, herpes simplex and varicella-zoster virus. Although all three viruses interact with LC during initial infection, the effects can be quite different, reflecting differences in biology and pathogenesis. Key words: Dendritic cells Á Langerhans cells Á Infectious diseases Á HIV Á HerpesvirusesSee accompanying mini-review by Kaplan et al. Biology of LC and interactions with virusesThe resident epidermal dendritic cells (DC), Langerhans cells (LC), form a tight network with each other and with the surrounding keratinocytes via E-cadherin in the skin or mucosal stratified squamous epithelium. In the anogenital region they are distributed throughout the anogenital skin and mucosa including vagina, ectocervix as well as male foreskin. In stratified squamous epithelium, LC overlie interstitial or dermal DC [1]. LC can repopulate from local and blood-borne precursors (reviewed by Kaplan et al. in this issue [2]). Similar to other myeloid DC, LC are able to bridge innate and adaptive immunity. They are able to interact directly with microorganisms at the periphery to produce effector cytokines and initiate or restimulate activation of T and B lymphocytes through antigen presentation. LC express different pattern recognition receptors such as C-type lectin receptors (CLR) and Toll-like receptors (TLR), to bind and capture pathogens. These interactions result in activation of intracellular signalling pathways leading to LC activation and cytokine induction. The CLR expressed by skin DC differ by site: Langerin by epidermal LC and DC-SIGN and mannose receptor by dermal DC. LC like other migratory DC are in an immature, highly endocytic state while sessile in the skin/mucosa. However after pathogen binding to TLR and uptake, LC become mature and migratory, downregulating their endocytic and antigen processing capacity. Mature LC migrate to the lymph nodes where they are directly or indirectly involved in presentation of pathogenderived antigens on MHC Class I and II to T cells, resulting in activation of antigen-specific T cells [2][3][4]. Recent studies have raised the possibility that LC may have an immunosuppressive role [5][6][7]. Kaplan et al. [2] showed that contact hypersensitivity was amplified on LC ablation, while Cumberbatch et al.[5] found defective LC mobilisation in patients with psoriasis. Immunosuppression rather than stimulation could be explained, in part, by the maturational process associated with LC migration during steady-state conditions. Jian...

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“…Post polymerase chain reaction (PCR) ligase detection reaction (LDR) analyses were used to genotype CCR5 promoter SNPs-2733, -2554, -2459, -2135, -2132, -2086, and -1835. Complete details of this genotyping strategy have been described in Kawamura et al [20].…”

Section: Dna Preparation and Genotyping Of Ccr5 Orf And Ccr5 Promotermentioning

confidence: 99%

CCR5 promoter polymorphism determines macrophage CCR5 density and magnitude of HIV-1 propagation in vitro

Salkowitz

Bruse

Meyerson

et al. 2003

Clinical Immunology

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R5 HIV productively infects Langerhans cells, and infection levels are regulated by compoundCCR5polymorphisms

Cited by 177 publications

References 50 publications

Parallel Loss of Myeloid and Plasmacytoid Dendritic Cells from Blood and Lymphoid Tissue in Simian AIDS

Parallel Loss of Myeloid and Plasmacytoid Dendritic Cells from Blood and Lymphoid Tissue in Simian AIDS

Langerhans cells and viral immunity

CCR5 promoter polymorphism determines macrophage CCR5 density and magnitude of HIV-1 propagation in vitro

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