Oral mucosal Langerhans’ cells as target, effector and vector in HIV infection

Chou, Li‐Fang; Epstein, Judith E.; Cassol, Sharon; West, D.M.; He, Wenhua; Firth, James D.

doi:10.1034/j.1600-0714.2000.290805.x

Cited by 46 publications

(51 citation statements)

References 29 publications

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“…Consistent with these impairments of DCs in the Tg mice, defective terminal differentiation of oral Langerhans' cells was demonstrated in human HIV infection by decreased expression of MHC class II Ags (9, 10), as well as the presence of blunt dendrites, limited development of organelles, and lack of Birbeck granules (10). Furthermore, numbers of both oral (8,28) and esophageal (29) Langerhans' cells are depleted in HIV infection.…”

Section: Discussionmentioning

confidence: 99%

Altered CD4+ T Cell Phenotype and Function Determine the Susceptibility to Mucosal Candidiasis in Transgenic Mice Expressing HIV-1

Lewandowski¹,

Marquis²,

Aumont³

et al. 2006

The Journal of Immunology

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The impairments of protective mucosal immunity which cause susceptibility to oropharyngeal candidiasis (OPC) in HIV infection remain undefined. This study used a model of OPC in CD4C/HIV MutA transgenic (Tg) mice expressing Rev, Env, and Nef of HIV-1 to investigate the role of transgene expressing dendritic cells (DCs) and CD4+ T cells in maintenance of chronic oral carriage of Candida albicans. DCs were depleted in the Tg mice and had an immature phenotype, with low expression of MHC class II and IL-12. CD4+ T cells were quantitatively reduced in the oral mucosa, cervical lymph nodes (CLNs) and peripheral blood of the Tg mice, and displayed a polarization toward a nonprotective Th2 response. Proliferation of CLN CD4+ T cells from infected Tg mice in response to C. albicans Ag in vitro was abrogated and the cells failed to acquire an effector phenotype. Coculture of C. albicans-pulsed DCs with CD4+ T cells in vitro showed that Tg expression in either or both of these cell populations sharply reduced the proliferation of CD4+ T cells and their production of IL-2. Finally, transfer of naive non-Tg CD4+ T cells into these Tg mice restored proliferation to C. albicans Ag and sharply reduced oral burdens of C. albicans. Overall, these results indicate that defective CD4+ T cells primarily determine the susceptibility to chronic carriage of C. albicans in these Tg mice.

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Section: Discussionmentioning

confidence: 99%

Altered CD4+ T Cell Phenotype and Function Determine the Susceptibility to Mucosal Candidiasis in Transgenic Mice Expressing HIV-1

Lewandowski¹,

Marquis²,

Aumont³

et al. 2006

The Journal of Immunology

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“…Indeed, HIV-1-activated DCs express CCR7 and may relocate to the secondary lymphoid organs where HIV-1 replication is the most active. CD11c ϩ DCs have been shown to be one of the first mucosal cells targeted during oral and sexual transmission (9,16,31,50). They capture HIV through C-type lectin (e.g., DC-SIGN, mannose receptor)-dependent and -independent pathways, thereby promoting the subsequent transmission of virus to CD4 ϩ T cells (26,27).…”

Section: Discussionmentioning

confidence: 99%

Human Immunodeficiency Virus Type 1 Activates Plasmacytoid Dendritic Cells and Concomitantly Induces the Bystander Maturation of Myeloid Dendritic Cells

Fonteneau

Larsson²,

Beignon³

et al. 2004

J Virol

302

310

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In this study, we analyzed the phenotypic and physiological consequences of the interaction of plasmacytoid dendritic cells (pDCs) with human immunodeficiency virus type 1 (HIV-1). pDCs are one cellular target of HIV-1 and respond to the virus by producing alpha/beta interferon (IFN-␣/␤) and chemokines. The outcome of this interaction, notably on the function of bystander myeloid DC (CD11c ؉ DCs), remains unclear. We therefore evaluated the effects of HIV-1 exposure on these two DC subsets under various conditions. Bloodpurified pDCs and CD11c ؉ DCs were exposed in vitro to HIV-1, after which maturation markers, cytokine production, migratory capacity, and CD4 T-cell stimulatory capacity were analyzed. pDCs exposed to different strains of infectious or even chemically inactivated, nonreplicating HIV-1 strongly upregulated the expression of maturation markers, such as CD83 and functional CCR7, analogous to exposure to R-848, a synthetic agonist of toll-like receptor-7 and -8. In addition, HIV-1-activated pDCs produced cytokines (IFN-␣ and tumor necrosis factor alpha), migrated in response to CCL19 and, in coculture, matured CD11c ؉ DCs, which are not directly activated by HIV. pDCs also acquired the ability to stimulate naïve CD4 ؉ T cells, albeit less efficiently than CD11c ؉ DCs. This HIV-1-induced maturation of both DC subsets may explain their disappearance from the blood of patients with high viral loads and may have important consequences on HIV-1 cellular transmission and HIV-1-specific T-cell responses.

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“…C. albicans-specific T-cell activation by human epidermal Langerhans' cells (85,223) requires not only the ligation of the T-cell receptor to the antigen-MHC complex but also costimulation by the combination of adhesion molecules CD54 and CD58 with CD11a and CD2 on T cells, respectively (433). As described in further detail below, productive infection of oral mucosal Langerhans' cells by HIV-1 may contribute to their selective depletion (81) and perturb their ability to generate a primary immune response (44), which may impair protective mucosal immunity against colonization and infection by opportunistic microbial pathogens. In addition, Langerhans' cells serve as the portal of entry for HIV-1 at mucosal sites and are critical to the initiation and subsequent spread of infection to draining lymphoid tissue (340).…”

Section: Moreover Il-2 (But Not Gamma Interferon [Ifn-␥])-activated Cd8mentioning

confidence: 99%

“…Mucosal Langerhans' cells are the initial target cells after primary mucosal contact with the virus, facilitating the transfer of HIV to CD4 ϩ cells (81,340,341). Tonsils and adenoids from HIV-infected patients contain multinucleated syncytia expressing high levels of intracellular HIV Gag protein in the DC-and T-cell-rich crypt lymphoepithelium (164,165).…”

Section: Perturbed Mucosal Immune Defense Mechanisms Against C Albicmentioning

confidence: 99%

Immunopathogenesis of Oropharyngeal Candidiasis in Human Immunodeficiency Virus Infection

2004

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Oropharyngeal and esophageal candidiases remain significant causes of morbidity in human immunodeficiency virus (HIV)-infected patients, despite the dramatic ability of antiretroviral therapy to reconstitute immunity. Notable advances have been achieved in understanding, at the molecular level, the relationships between the progression of HIV infection, the acquisition, maintenance, and clonality of oral candidal populations, and the emergence of antifungal resistance. However, the critical immunological defects which are responsible for the onset and maintenance of mucosal candidiasis in patients with HIV infection have not been elucidated. The devastating impact of HIV infection on mucosal Langerhans' cell and CD4+ cell populations is most probably central to the pathogenesis of mucosal candidiasis in HIV-infected patients. However, these defects may be partly compensated by preserved host defense mechanisms (calprotectin, keratinocytes, CD8+ T cells, and phagocytes) which, individually or together, may limit Candida albicans proliferation to the superficial mucosa. The availability of CD4C/HIV transgenic mice expressing HIV-1 in immune cells has provided the opportunity to devise a novel model of mucosal candidiasis that closely mimics the clinical and pathological features of candidal infection in human HIV infection. These transgenic mice allow, for the first time, a precise cause-and-effect analysis of the immunopathogenesis of mucosal candidiasis in HIV infection under controlled conditions in a small laboratory animal

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Oral mucosal Langerhans’ cells as target, effector and vector in HIV infection

Cited by 46 publications

References 29 publications

Altered CD4+ T Cell Phenotype and Function Determine the Susceptibility to Mucosal Candidiasis in Transgenic Mice Expressing HIV-1

Altered CD4+ T Cell Phenotype and Function Determine the Susceptibility to Mucosal Candidiasis in Transgenic Mice Expressing HIV-1

Human Immunodeficiency Virus Type 1 Activates Plasmacytoid Dendritic Cells and Concomitantly Induces the Bystander Maturation of Myeloid Dendritic Cells

Immunopathogenesis of Oropharyngeal Candidiasis in Human Immunodeficiency Virus Infection

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