C-type lectin Langerin is a β-glucan receptor on human Langerhans cells that recognizes opportunistic and pathogenic fungi

Jong, Marein A. W. P. de; Vriend, Lianne; Theelen, Bart; Taylor, Maureen E.; Fluitsma, Donna; Boekhout, Teun; Geijtenbeek, Teunis B. H.

doi:10.1016/j.molimm.2009.12.016

Cited by 120 publications

(117 citation statements)

References 41 publications

Supporting

Mentioning

116

Contrasting

Order By: Relevance

“…These data support a function for langerin as a pattern-recognition receptor (39) for different pathogens, including viruses, such as HIV-1, HSV type 1 (data not shown), and HSV-2, fungi, and bacteria (15,(30)(31)(32)(33). The function of langerin as a pattern-recognition receptor is unclear.…”

Section: Discussionmentioning

confidence: 60%

See 1 more Smart Citation

Herpes Simplex Virus Type 2 Enhances HIV-1 Susceptibility by Affecting Langerhans Cell Function

Jong

Witte

Taylor

et al. 2010

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Genital herpes is the most prevalent viral sexually transmitted infection worldwide and is mainly caused by HSV type 2 (HSV-2). HSV-2 infection enhances HIV-1 susceptibility, even in the absence of clinical symptoms. In this study, we investigated the effect of HSV-2 on HIV-1 transmission by mucosal Langerhans cells (LCs). LCs are important in heterosexual transmission because they form a barrier against HIV-1 infection; LCs efficiently capture and degrade HIV-1 through the C-type lectin langerin, thereby preventing HIV-1 transmission. Notably, our data showed that HSV-2 enhanced HIV-1 infection of LCs and subsequent HIV-1 transmission to T cells. HSV-2 interfered with HIV-1 capture by langerin, which allowed efficient HIV-1 infection of LCs. HSV-2 inhibited the antiviral function of langerin at two levels; HSV-2 decreased langerin expression and competed with HIV-1 for langerin binding. HSV-2 replication was not required, because both UV-inactivated HSV-2 and TLR-3 agonist polyinosinic:polycytidylic acid similarly increased HIV-1 transmission by LCs. Therefore, we identified a mechanism by which HSV-2 enhances HIV-1 susceptibility, even in the absence of clinical symptoms. Our data demonstrated that viral coinfections, such as HSV-2, breach the protective function of LCs by abrogating langerin function, which increases HIV-1 susceptibility. These data reinforce the importance of preventing sexually transmitted infections, such as HSV-2, to reduce the transmission of HIV-1.

show abstract

Section: Discussionmentioning

confidence: 60%

“…Langerin interacts with different pathogens, such as HIV-1, Candida albicans, and Mycobacterium (15,(30)(31)(32)(33). Therefore, we investigated whether HSV-2 interacts with langerin and, thereby, competes with HIV-1 for the carbohydrate-recognition domain of langerin.…”

Section: Hsv-2 Competes With Hiv-1 For Langerin Bindingmentioning

confidence: 99%

Herpes Simplex Virus Type 2 Enhances HIV-1 Susceptibility by Affecting Langerhans Cell Function

Jong

Witte

Taylor

et al. 2010

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Langerin recognizes mannose-rich sugars expressed by bacterial and fungal pathogens, such as Mycobacterium spp. (16) and Candida albicans (17), and some viruses. Human immunodeficiency virus type 1(HIV-1) is recognized by a variety of CLRs, including DC-SIGN, MMR, and langerin (18,19).…”

mentioning

confidence: 99%

The C-type Lectin Langerin Functions as a Receptor for Attachment and Infectious Entry of Influenza A Virus

Londrigan

Nasr

et al. 2016

J Virol

View full text Add to dashboard Cite

It is well established that influenza A virus (IAV) attachment to and infection of epithelial cells is dependent on sialic acid (SIA)at the cell surface, although the specific receptors that mediate IAV entry have not been defined and multiple receptors may exist. Lec2 Chinese hamster ovary (CHO) cells are SIA deficient and resistant to IAV infection. Here we demonstrate that the expression of the C-type lectin receptor langerin in Lec2 cells (Lec2-Lg) rendered them permissive to IAV infection, as measured by replication of the viral genome, transcription of viral mRNA, and synthesis of viral proteins. Unlike SIA-dependent infection of parental CHO cells, IAV attachment and infection of Lec2-Lg cells was mediated via lectin-mediated recognition of mannoserich glycans expressed by the viral hemagglutinin glycoprotein. Lec2 cells expressing endocytosis-defective langerin bound IAV efficiently but remained resistant to IAV infection, confirming that internalization via langerin was essential for infectious entry. Langerin-mediated infection of Lec2-Lg cells was pH and dynamin dependent, occurred via clathrin-and caveolin-mediated endocytic pathways, and utilized early (Rab5 ؉ ) but not late (Rab7 ؉ ) endosomes. This study is the first to demonstrate that langerin represents an authentic receptor that binds and internalizes IAV to facilitate infection. Moreover, it describes a unique experimental system to probe specific pathways and compartments involved in infectious entry following recognition of IAV by a single cell surface receptor. IMPORTANCE On the surface of host cells, sialic acid (SIA) functions as the major attachment factor for influenza A viruses (IAV). However, few studies have identified specific transmembrane receptors that bind and internalize IAV to facilitate infection. Here we identify human langerin as a transmembrane glycoprotein that can act as an attachment factor and a bone fide endocytic receptor for IAV infection. Expression of langerin by an SIA-deficient cell line resistant to IAV rendered cells permissive to infection. As langerin represented the sole receptor for IAV infection in this system, we have defined the pathways and compartments involved in infectious entry of IAV into cells following recognition by langerin. Influenza A viruses (IAV) enter and infect cells in a pH-dependent manner. In humans, epithelial cells lining the respiratory tract are the primary targets of IAV infection and support productive replication, resulting in virus amplification and spread. Seasonal IAV also infect airway macrophages (M) and dendritic cells (DC), generally resulting in abortive replication, although virulent strains such as highly pathogenic avian influenza can replicate productively in these cells (reviewed in reference 1).It is generally accepted that binding of the IAV hemagglutinin (HA) to sialic acid (SIA) residues expressed at the cell surface is the first step in initiating infectious entry; however, binding to SIA residues per se does not induce virus internalization. Rather,...

show abstract

“…To recognize pathogens, LCs express a broad repertoire of pattern recognition receptors, such as TLRs and C-type lectin receptors (CLRs). In particular, human LCs express the CLR langerin (5), which interacts with viruses, bacteria and fungi (1,(6)(7)(8). Some CLRs have been shown to function as cellular adhesion molecules by recognizing proteoglycans or glycoproteins on autologous cells (9,10).…”

mentioning

confidence: 99%

“…Langerin recognizes the monosaccharides mannose, fucose, and N-acetylglucosamine (GlcNAc) and the oligosaccharides mannan and b-glucan (6,12). This carbohydrate specificity of langerin allows recognition of different pathogens such as mycobacteria (13), Candida species (6), Measles virus (MV) (14), and HIV-1 (1,4).…”

mentioning

confidence: 99%

Langerhans Cell–Dendritic Cell Cross-Talk via Langerin and Hyaluronic Acid Mediates Antigen Transfer and Cross-Presentation of HIV-1

Berg

Cardinaud

Aar

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

Human epidermal and mucosal Langerhans cells (LCs) express the C-type lectin receptor langerin that functions as a pattern recognition receptor. LCs are among the first immune cells to interact with HIV-1 during sexual transmission. In this study, we demonstrate that langerin not only functions as a pattern recognition receptor but also as an adhesion receptor mediating clustering between LCs and dendritic cells (DCs). Langerin recognized hyaluronic acid on DCs and removal of these carbohydrate structures partially abrogated LC–DC clustering. Because LCs did not cross-present HIV-1–derived Ags to CD8+ T cells in a cross-presentation model, we investigated whether LCs were able to transfer Ags to DCs. LC–DC clustering led to maturation of DCs and facilitated Ag transfer of HIV-1 to DCs, which subsequently induced activation of CD8+ cells. The rapid transfer of Ags to DCs, in contrast to productive infection of LCs, suggests that this might be an important mechanism for induction of anti–HIV-1 CD8+ T cells. Induction of the enzyme hyaluronidase-2 by DC maturation allowed degradation of hyaluronic acid and abrogated LC–DC interactions. Thus, we have identified an important function of langerin in mediating LC–DC clustering, which allows Ag transfer to induce CTL responses to HIV-1. Furthermore, we showed this interaction is mediated by hyaluronidase-2 upregulation after DC maturation. These data underscore the importance of LCs and DCs in orchestrating adaptive immunity to HIV-1. Novel strategies might be developed to harness this mechanism for vaccination.

show abstract

C-type lectin Langerin is a β-glucan receptor on human Langerhans cells that recognizes opportunistic and pathogenic fungi

Cited by 120 publications

References 41 publications

Herpes Simplex Virus Type 2 Enhances HIV-1 Susceptibility by Affecting Langerhans Cell Function

Herpes Simplex Virus Type 2 Enhances HIV-1 Susceptibility by Affecting Langerhans Cell Function

The C-type Lectin Langerin Functions as a Receptor for Attachment and Infectious Entry of Influenza A Virus

Langerhans Cell–Dendritic Cell Cross-Talk via Langerin and Hyaluronic Acid Mediates Antigen Transfer and Cross-Presentation of HIV-1

Contact Info

Product

Resources

About