Immunological function of Langerhans cells in HIV infection

Matsuzawa, Takamitsu; Ogawa, Youichi; Moriishi, Kohji; Shimada, Shinji; Kawamura, Tatsuyoshi

doi:10.1016/j.jdermsci.2017.03.015

Cited by 13 publications

(11 citation statements)

References 59 publications

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“…Cervicovaginal epithelial cell secretion of MIP-3α has been shown to attract Langerhans cells (Cremel et al, 2005;Berlier et al, 2006), which although controversial, have been proposed to act as a "Trojan horse" facilitating HIV dissemination to lymph nodes (Cavrois et al, 2008;Matsuzawa et al, 2017). In this regard, the effect of L-LA on dampening MIP-3α production may also be important for inhibiting HIV transmission.…”

Section: Discussionmentioning

confidence: 99%

Distinct Immune Responses Elicited From Cervicovaginal Epithelial Cells by Lactic Acid and Short Chain Fatty Acids Associated With Optimal and Non-optimal Vaginal Microbiota

Delgado-Diaz

Tyssen

Hayward

et al. 2020

Front. Cell. Infect. Microbiol.

114

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Non-optimal vaginal microbiota, as observed in bacterial vaginosis (BV), is typically characterized by a depletion of beneficial lactobacilli and an abundance of numerous anaerobes. These non-optimal conditions are associated with subclinical cervicovaginal inflammation and an increased risk of HIV infection compared to women colonized with optimal vaginal microbiota dominated by lactobacilli. Lactic acid (LA) is a major organic acid metabolite produced by vaginal lactobacilli that elicits anti-inflammatory effects from cervicovaginal epithelial cells and is dramatically depleted during BV. However, it is unclear if LA retains its anti-inflammatory activity in the presence of vaginal microbiota metabolites comprising short chain fatty acids (SCFAs) and succinic acid, which are also produced by an optimal vaginal microbiota. Furthermore, the immunomodulatory effect of SCFAs and succinic acid on cervicovaginal epithelial cells at higher concentrations present during BV is unknown. Here we report that in the presence of physiologically relevant concentrations of SCFAs and succinic acid at pH 3.9 (as found in women with lactobacillus-dominated microbiota) LA induced an anti-inflammatory state in cervicovaginal epithelial cells and inhibited inflammation elicited by the toll-like receptor (TLR) agonists polyinosinic:polycytidylic acid and Pam3CSK4. When cervicovaginal epithelial cells were treated with a vaginal microbiota metabolite mixture representative of BV, containing a lower concentration of LA but higher concentrations of SCFA/succinic acid at pH 7, no anti-inflammatory was observed. Rather, the vaginal microbiota metabolite mixture representative of BV dysregulated the immune response of cervicovaginal epithelial cells during prolonged and sustained treatments. This was evidenced by increased basal and TLR-induced production of pro-inflammatory cytokines including tumor necrosis factor-α, but decreased basal production of chemokines including RANTES and IP-10. Further characterization of individual components of the BV vaginal microbiota mixture suggested that acetic acid is an important vaginal microbiota metabolite capable of eliciting diverse Delgado-Diaz et al. Immunomodulation by Vaginal Microbial Metabolites immunomodulatory effects on a range of cervicovaginal epithelial cell targets. These findings indicate that elevated levels of SCFAs are a potential source of cervicovaginal inflammation in women experiencing BV, and support the unique anti-inflammatory properties of LA on cervicovaginal epithelial cells as well as a role for LA or LA-producing lactobacilli to reverse genital inflammation associated with increased HIV risk.

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Section: Discussionmentioning

confidence: 99%

Distinct Immune Responses Elicited From Cervicovaginal Epithelial Cells by Lactic Acid and Short Chain Fatty Acids Associated With Optimal and Non-optimal Vaginal Microbiota

Delgado-Diaz

Tyssen

Hayward

et al. 2020

Front. Cell. Infect. Microbiol.

114

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“…Mucosal surfaces are the first entry site for HIV during transmission (Figure 1). Indeed, Langerhans cells (LCs), urethral macrophages and/or conventional DCs residing in mucosal tissues have been proposed to capture HIV (178)(179)(180)(181)(182)(183)(184)(185) and further replicate or transfer the virus locally to potential HIV target cells, such as macrophages and CD4 + T cells (Figure 1). NK cells, macrophages and DCs, which are the effector cells involved in Fc-mediated Ab functions, are present in different mucosal tissues at different levels.…”

Section: Roles Of Fc-mediated Antibody Functions In Mucosal Tissuesmentioning

confidence: 99%

Update on Fc-Mediated Antibody Functions Against HIV-1 Beyond Neutralization

Dispinseri

Iannone

et al. 2019

Front. Immunol.

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Antibodies (Abs) are the major component of the humoral immune response and a key player in vaccination. The precise Ab-mediated inhibitory mechanisms leading to in vivo protection against HIV have not been elucidated. In addition to the desired viral capture and neutralizing Ab functions, complex Ab-dependent mechanisms that involve engaging immune effector cells to clear infected host cells, immune complexes, and opsonized virus have been proposed as being relevant. These inhibitory mechanisms involve Fc-mediated effector functions leading to Ab-dependent cellular cytotoxicity, phagocytosis, cell-mediated virus inhibition, aggregation, and complement inhibition. Indeed, the decreased risk of infection observed in the RV144 HIV-1 vaccine trial was correlated with the production of non-neutralizing inhibitory Abs, highlighting the role of Ab inhibitory functions besides neutralization. Moreover, Ab isotypes and subclasses recognizing specific HIV envelope epitopes as well as pecular Fc-receptor polymorphisms have been associated with disease progression. These findings further support the need to define which Fc-mediated Ab inhibitory functions leading to protection are critical for HIV vaccine design. Herein, based on our previous review Su & Moog Front Immunol 2014, we update the different inhibitory properties of HIV-specific Abs that may potentially contribute to HIV protection.

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“…This can lead to transmission and rapid spread of the infection to CD4+ T cells through cell-to-cell interactions [ 42 ]. Considering the impact of HIV in DCs compared to LCs, HIV-primed monocyte-derived LCs lead to a higher amount of HIV-specific CD8+ T cells being induced, as well as a lowered induction of Tregs compared to HIV-primed monocyte-derived DCs [ 43 ].…”

Section: Hiv and Dendritic Cellsmentioning

confidence: 99%

The Role of Dendritic Cells in TB and HIV Infection

Abrahem

Chiang

Haquang

et al. 2020

JCM

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Dendritic cells are the principal antigen-presenting cells (APCs) in the host defense mechanism. An altered dendritic cell response increases the risk of susceptibility of infections, such as Mycobacterium tuberculosis (M. tb), and the survival of the human immunodeficiency virus (HIV). The altered response of dendritic cells leads to decreased activity of T-helper-1 (Th1), Th2, Regulatory T cells (Tregs), and Th17 cells in tuberculosis (TB) infections due to a diminishment of cytokine release from these APCs, while HIV infection leads to DC maturation, allowing DCs to migrate to lymph nodes and the sub-mucosa where they then transfer HIV to CD4 T cells, although there is controversy around this topic. Increases in the levels of the antioxidant glutathione (GSH) plays a critical role in maintaining dendritic cell redox homeostasis, leading to an adequate immune response with sufficient cytokine release and a subsequent robust immune response. Thus, an understanding of the intricate pathways involved in the dendritic cell response are needed to prevent co-infections and co-morbidities in individuals with TB and HIV.

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Immunological function of Langerhans cells in HIV infection

Abstract: HIV-primed LCs trigger beneficial immune responses against HIV infection through the increased induction of HIV-specific CD8 T cells and the decreased induction of effector Tregs in the initial phase of HIV infection, thereby contributing to the prolonged onset of AIDS.

Cited by 13 publications

References 59 publications

Distinct Immune Responses Elicited From Cervicovaginal Epithelial Cells by Lactic Acid and Short Chain Fatty Acids Associated With Optimal and Non-optimal Vaginal Microbiota

Distinct Immune Responses Elicited From Cervicovaginal Epithelial Cells by Lactic Acid and Short Chain Fatty Acids Associated With Optimal and Non-optimal Vaginal Microbiota

Update on Fc-Mediated Antibody Functions Against HIV-1 Beyond Neutralization

The Role of Dendritic Cells in TB and HIV Infection

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