Myeloid C-Type Lectin Receptors in Viral Recognition and Antiviral Immunity

Monteiro, João Tiago Silva; Lepenies, Bernd

doi:10.3390/v9030059

Cited by 71 publications

(68 citation statements)

References 160 publications

(233 reference statements)

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“…Different CLRs possess the capacity to activate various innate signaling pathways that give rise to specific types of cellular immune responses (Figure 2 ) ( 74 ). However, viruses contain the capacity to alter CLR-induced signaling, thereby inhibiting induction of type I IFN responses ( 75 ).…”

Section: Shaping Antiviral Innate Immune Responses By Clrsmentioning

confidence: 99%

“…C-type lectin receptors are important in inducing and modulating immunity (Figure 2 ). Some CLRs contain immunoreceptor tyrosine-based activation motifs (ITAMs), hemi-ITAMs, or immunoreceptor tyrosine-based inhibitory motifs (ITIMs), whereas some do not contain any obvious signaling motifs ( 75 ). Dectin-2, DCAR, and MDL-1 belong to the ITAM-containing CLRs, whereas DCIR contains an ITIM.…”

Section: Shaping Antiviral Innate Immune Responses By Clrsmentioning

confidence: 99%

“…Dectin-2, DCAR, and MDL-1 belong to the ITAM-containing CLRs, whereas DCIR contains an ITIM. Dectin-1 belongs to the hemi-ITAM group, and other CLRs such as DC-SIGN, MR, and DEC-205 do not contain any known ITAMs or ITIMs ( 75 ). DCIR is expressed by DCs and macrophages, and contains an ITIM that mediates inhibitory signals by recruiting phosphatases SH2-domain-containing protein tyrosine phosphatase 1 (SHP1) or SHP2 after receptor ligation ( 86 ).…”

Section: Shaping Antiviral Innate Immune Responses By Clrsmentioning

confidence: 99%

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C-Type Lectin Receptors in Antiviral Immunity and Viral Escape

et al. 2018

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C-type lectin receptors (CLRs) are important pattern recognition receptors involved in recognition and induction of adaptive immunity to pathogens. Certain CLRs play an important role in viral infections as they efficiently interact with viruses. However, it has become clear that deadly viruses subvert the function of CLRs to escape antiviral immunity and promote infection. In particular, viruses target CLRs to suppress or modulate type I interferons that play a central role in the innate and adaptive defense against viruses. In this review, we discuss the function of CLRs in binding to enveloped viruses like HIV-1 and Dengue virus, and how uptake and signaling cascades have decisive effects on the outcome of infection.

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Section: Shaping Antiviral Innate Immune Responses By Clrsmentioning

confidence: 99%

Section: Shaping Antiviral Innate Immune Responses By Clrsmentioning

confidence: 99%

Section: Shaping Antiviral Innate Immune Responses By Clrsmentioning

confidence: 99%

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C-Type Lectin Receptors in Antiviral Immunity and Viral Escape

et al. 2018

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“…The main function of CLRs is the recognition of highly conserved glycans and glycoproteins located on the surface of pathogens including viruses, parasites, fungi, and bacteria ( 3 , 7 – 9 ). However, CLRs may also sense endogenous danger signals released by damaged and necrotic cells ( 10 – 13 ).…”

Section: Introductionmentioning

confidence: 99%

C-Type Lectin Receptor (CLR)–Fc Fusion Proteins As Tools to Screen for Novel CLR/Bacteria Interactions: An Exemplary Study on Preselected Campylobacter jejuni Isolates

et al. 2018

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C-type lectin receptors (CLRs) are carbohydrate-binding receptors that recognize their ligands often in a Ca2+-dependent manner. Upon ligand binding, myeloid CLRs in innate immunity trigger or inhibit a variety of signaling pathways, thus initiating or modulating effector functions such as cytokine production, phagocytosis, and antigen presentation. CLRs bind to various pathogens, including viruses, fungi, parasites, and bacteria. The bacterium Campylobacter jejuni (C. jejuni) is a very frequent Gram-negative zoonotic pathogen of humans, causing severe intestinal symptoms. Interestingly, C. jejuni expresses several glycosylated surface structures, for example, the capsular polysaccharide (CPS), lipooligosaccharide (LOS), and envelope proteins. This “Methods” paper describes applications of CLR–Fc fusion proteins to screen for yet unknown CLR/bacteria interactions using C. jejuni as an example. ELISA-based detection of CLR/bacteria interactions allows a first prescreening that is further confirmed by flow cytometry-based binding analysis and visualized using confocal microscopy. By applying these methods, we identified Dectin-1 as a novel CLR recognizing two selected C. jejuni isolates with different LOS and CPS genotypes. In conclusion, the here-described applications of CLR–Fc fusion proteins represent useful methods to screen for and identify novel CLR/bacteria interactions.

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“…The C-type lectin receptors (CLRs) also belong to PRRs and recognize predominantly carbohydrates and non-carbohydrates through mechanisms that are still not fully understood ( 22 ). The CLR Dectin-1 recognizes β-glucans ( 22 – 25 ) that naturally occur in the cell wall of fungi ( 23 ). In addition to pathogen-derived factors, endogenous N -glycans present on the surface of tumor cells also represent potential Dectin-1 ligands and trigger tumor killing by NK cells ( 26 ).…”

Section: Introductionmentioning

confidence: 99%

Dectin-1 Positive Dendritic Cells Expand after Infection with Leishmania major Parasites and Represent Promising Targets for Vaccine Development

et al. 2018

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Resistant mouse strains mount a protective T cell-mediated immune response upon infection with Leishmania (L.) parasites. Healing correlates with a T helper (Th) cell-type 1 response characterized by a pronounced IFN-γ production, while susceptibility is associated with an IL-4-dependent Th2-type response. It has been shown that dermal dendritic cells are crucial for inducing protective Th1-mediated immunity. Additionally, there is growing evidence that C-type lectin receptor (CLR)-mediated signaling is involved in directing adaptive immunity against pathogens. However, little is known about the function of the CLR Dectin-1 in modulating Th1- or Th2-type immune responses by DC subsets in leishmaniasis. We characterized the expression of Dectin-1 on CD11c+ DCs in peripheral blood, at the site of infection, and skin-draining lymph nodes of L. major-infected C57BL/6 and BALB/c mice and in peripheral blood of patients suffering from cutaneous leishmaniasis (CL). Both mouse strains responded with an expansion of Dectin-1+ DCs within the analyzed tissues. In accordance with the experimental model, Dectin-1+ DCs expanded as well in the peripheral blood of CL patients. To study the role of Dectin-1+ DCs in adaptive immunity against L. major, we analyzed the T cell stimulating potential of bone marrow-derived dendritic cells (BMDCs) in the presence of the Dectin-1 agonist Curdlan. These experiments revealed that Curdlan induces the maturation of BMDCs and the expansion of Leishmania-specific CD4+ T cells. Based on these findings, we evaluated the impact of Curdlan/Dectin-1 interactions in experimental leishmaniasis and were able to demonstrate that the presence of Curdlan at the site of infection modulates the course of disease in BALB/c mice: wild-type BALB/c mice treated intradermally with Curdlan developed a protective immune response against L. major whereas Dectin-1−/− BALB/c mice still developed the fatal course of disease after Curdlan treatment. Furthermore, the vaccination of BALB/c mice with a combination of soluble L. major antigens and Curdlan was able to provide a partial protection from severe leishmaniasis. These findings indicate that the ligation of Dectin-1 on DCs acts as an important checkpoint in adaptive immunity against L. major and should therefore be considered in future whole-organism vaccination strategies.

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Myeloid C-Type Lectin Receptors in Viral Recognition and Antiviral Immunity

Cited by 71 publications

References 160 publications

C-Type Lectin Receptors in Antiviral Immunity and Viral Escape

C-Type Lectin Receptors in Antiviral Immunity and Viral Escape

C-Type Lectin Receptor (CLR)–Fc Fusion Proteins As Tools to Screen for Novel CLR/Bacteria Interactions: An Exemplary Study on Preselected Campylobacter jejuni Isolates

Dectin-1 Positive Dendritic Cells Expand after Infection with Leishmania major Parasites and Represent Promising Targets for Vaccine Development

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