Initial Events in Establishing Vaginal Entry and Infection by Human Immunodeficiency Virus Type-1

Hladik, Florian; Sakchalathorn, Polachai; Ballweber, Lamar; Lentz, Gretchen M.; Fialkow, Michael; Eschenbach, David A.; McElrath, M. Juliana

doi:10.1016/j.immuni.2007.01.007

Cited by 430 publications

(468 citation statements)

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“…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]. The latter suggests that LC are transferring HIV to CD4 lymphocytes.…”

Section: Lc Interactions With Important Human Viruses Hiv and Lcmentioning

confidence: 99%

“…A role for LC has been long advocated as they are the major HIV infectable constitutive cell type in the anogenital stratified squamous epithelium. Several in vivo and ex vivo data support a role for LC infection in HIV-1 transmission [21,22]. Vaginal simian immunodeficiency virus (SIV) infection of Rhesus macaques resulted in infected LC beneath the vaginal epithelium within the first day of infection [22].…”

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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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Section: Lc Interactions With Important Human Viruses Hiv and Lcmentioning

confidence: 99%

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confidence: 99%

Langerhans cells and viral immunity

2008

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“…The CD4 molecules are expressed on epithelial and submucosal cells in both the upper and lower genital tracts of healthy women (5)(6)(7), and these cells include T lymphocytes, macrophages, dendritic cells (DCs), and Langerhans cells (8)(9)(10). The cells are all heterogeneous with regard to HIV susceptibility, which is critically dependent on the presence of the major HIV coreceptor CCR5 (7,(11)(12)(13)(14).…”

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confidence: 99%

“…The cells are all heterogeneous with regard to HIV susceptibility, which is critically dependent on the presence of the major HIV coreceptor CCR5 (7,(11)(12)(13)(14). Also, other classes of HIV-binding molecules, including the C-type lectin receptors (CLRs), have implications for HIV susceptibility and are present on mucosal macrophages and subpopulations of DCs.…”

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Stable CD4 Expression and Local Immune Activation in the Ectocervical Mucosa of HIV-Infected Women

Hirbod

Kimani

Tjernlund

et al. 2013

The Journal of Immunology

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Studies using genital tissue samples from HIV-infected women might provide important information about HIV susceptibility and transmission. In this study, ectocervical biopsies were obtained from 20 HIV-seropositive (HIV+) Kenyan female sex workers (FSW) and 20 HIV-seronegative lower risk (HIV− LR) women. To control for the impact of sex work, 20 HIV− FSW were also recruited. Immune molecules were assessed in situ by immunohistochemistry and for mRNA expression by quantitative PCR. The HIV+ women were reportedly infected for a median of 3 y (1–21 y), with a median viral load of 11,735 copies/ml (20–648,000 copies/ml). These women had significantly lower CD4 blood cell counts than the HIV− LR women but comparable levels of CD4 expression in ectocervix. Whereas cellular markers were similar between the HIV+ group and the HIV− LR women, the HIV-binding molecules CCR5, dendritic cell–specific intercellular adhesion molecule-3–grabbing nonintegrin, and mannose receptor as well as the inflammatory markers CD69, IFN-γ, IL-6, and IL-22 were significantly upregulated in the HIV+ group. As compared with the HIV− FSW women, the HIV+ women had significantly upregulated levels of CD4, CD3, CCR5, Langerin, dendritic cell–specific intercellular adhesion molecule-3–grabbing nonintegrin, and mannose receptor as well as inflammatory cytokines. The CD4 cell depletion previously seen in the gut mucosa of HIV-infected individuals was thus not observed in the ectocervical mucosa. Stable CD4 cell expression and local immune activation in the lower female genital tract may promote viral replication and genital shedding and increase the risk of sexual HIV transmission.

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“…Langerhans cells (LCs) are a subset of DCs that are, in humans, characterized by expression of CD1a, the C-type lectin Langerin and the presence of Birbeck granules [6]. LCs reside in the epidermis and stratified epithelial tissues [7][8][9]. Recently, we have shown that LCs form a barrier against HIV-1; LCs capture HIV-1 through Langerin, resulting in internalization of HIV-1 into Birbeck granules and preventing subsequent HIV-1 transmission [10].…”

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Human Langerhans cells capture measles virus through Langerin and present viral antigens to CD4⁺ T cells but are incapable of cross‐presentation

et al. 2011

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Langerhans cells (LCs) are a subset of DCs that reside in the upper respiratory tract and are ideally suited to sense respiratory virus infections. Measles virus (MV) is a highly infectious lymphotropic and myelotropic virus that enters the host via the respiratory tract. Here, we show that human primary LCs are capable of capturing MV through the C-type lectin Langerin. Both immature and mature LCs presented MV-derived antigens in the context of HLA class II to MV-specific CD4 1 T cells. Immature LCs were not susceptible to productive infection by MV and did not present endogenous viral antigens in the context of HLA class I. In contrast, mature LCs could be infected by MV and presented de novo synthesized viral antigens to MV-specific CD8 1 T cells. Notably, neither immature nor mature LCs were able to cross-present exogenous UV-inactivated MV or MV-infected apoptotic cells. The lack of direct infection of immature LCs, and the inability of both immature and mature LCs to crosspresent MV antigens, suggest that human LCs may not be directly involved in priming MV-specific CD8 1 T cells. Immune activation of LCs seems a prerequisite for MV infection of LCs and subsequent CD8 1 T-cell priming via the endogenous antigen presentation pathway. Eur. J. Immunol. 2011. 41: 2619-2631 DOI 10.1002 Immunity to infection 2619 molecules, a process referred to as cross-presentation which is thought to be important in both viral and tumor immunity [2,3]. It is becoming evident that different DC subsets have specialized functions in anti-viral immunity, e.g. by inducing preferentially CD4 1 or CD8 1 T-cell responses or by inducing innate immunity against pathogens [4,5]. Langerhans cells (LCs) are a subset of DCs that are, in humans, characterized by expression of CD1a, the C-type lectin Langerin and the presence of Birbeck granules [6]. LCs reside in the epidermis and stratified epithelial tissues [7][8][9]. Recently, we have shown that LCs form a barrier against HIV-1; LCs capture HIV-1 through Langerin, resulting in internalization of HIV-1 into Birbeck granules and preventing subsequent HIV-1 transmission [10]. However, little is known about the role of human LCs and Langerin in antigen presentation.Capture of exogenous antigens by LCs leads to induction of CD4 1 T-cell responses [11][12][13]. However, the ability of LCs to cross-present exogenous antigens to CD8 1 T cells has been debated [14][15][16][17]. Klechevsky et al. [13] have shown that in vitrogenerated human LCs from either CD34 1 cells or monocytes are capable of cross-presenting influenza-virus proteins to CD8 1 T cells. However, these in vitro-generated LCs might be different from primary immature LCs.Here, we have investigated the antigen capture and presentation capacity of human primary LCs during measles virus (MV) infection. MV is the causative agent of measles, which remains an important cause of morbidity and mortality in developing countries. MV is a lymphotropic and myelotropic virus and DCs have been implicated in its transmission [18,19]. MV is on...

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Initial Events in Establishing Vaginal Entry and Infection by Human Immunodeficiency Virus Type-1

Cited by 430 publications

References 34 publications

Langerhans cells and viral immunity

Langerhans cells and viral immunity

Stable CD4 Expression and Local Immune Activation in the Ectocervical Mucosa of HIV-Infected Women

Human Langerhans cells capture measles virus through Langerin and present viral antigens to CD4⁺ T cells but are incapable of cross‐presentation

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Initial Events in Establishing Vaginal Entry and Infection by Human Immunodeficiency Virus Type-1

Cited by 430 publications

References 34 publications

Langerhans cells and viral immunity

Langerhans cells and viral immunity

Stable CD4 Expression and Local Immune Activation in the Ectocervical Mucosa of HIV-Infected Women

Human Langerhans cells capture measles virus through Langerin and present viral antigens to CD4+ T cells but are incapable of cross‐presentation

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Human Langerhans cells capture measles virus through Langerin and present viral antigens to CD4⁺ T cells but are incapable of cross‐presentation