Functional CD169 on Macrophages Mediates Interaction with Dendritic Cells for CD8+ T Cell Cross-Priming

Dinther, Dieke van; Veninga, Henrike; Iborra, Salvador; Borg, Ellen G. F.; Hoogterp, Leoni; Olesek, Katarzyna; Beijer, Marieke R.; Schetters, Sjoerd; Kalay, Hakan; García-Vallejo, Juan J.; Franken, Kees L. M. C.; Cham, Lamin B.; Lang, Karl S.; Kooyk, Yvette van; Sancho, David; Crocker, Paul R.; Haan, Joke M. M. den

doi:10.1016/j.celrep.2018.01.021

Cited by 106 publications

(119 citation statements)

References 58 publications

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“…Interestingly, Siglec-1 + macrophages from the spleen marginal zone have been shown in the vesicular stomatitis virus (VSV) mouse model to support a locally restricted enforced viral replication by down-modulating type I IFN responsiveness thus providing a source of viral antigen required to elicit a protective immune response (46). Moreover, Siglec-1 + macrophages can transfer viral antigens to cDC1s which in turn cross-prime CD8 + T cell responses (47). Importantly, this antigen transfer was mediated by Siglec-1 on the macrophages interacting with sialylated proteins present on cDC1 cell surface (47).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, Siglec-1 + macrophages can transfer viral antigens to cDC1s which in turn cross-prime CD8 + T cell responses (47). Importantly, this antigen transfer was mediated by Siglec-1 on the macrophages interacting with sialylated proteins present on cDC1 cell surface (47). Thus, Siglec-1 expression may also confer blood pre-DCs the capacity to recruit and instruct the help of crosspresenting cDC1s.…”

Section: Discussionmentioning

confidence: 99%

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Constitutive Siglec-1 expression confers susceptibility to HIV-1 infection of human dendritic cell precursors

Ruffin

Gea‐Mallorquí

Brouiller

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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The human dendritic cell (DC) lineage has recently been unraveled by high-dimensional mapping, revealing the existence of a discrete new population of blood circulating DC precursors (pre-DCs). Whether this new DC population possesses specific functional features as compared to the other blood DC subset upon pathogen encounter remained to be evaluated. A unique feature of pre-DCs among blood DCs is their constitutive expression of the viral adhesion receptor Siglec-1. Here, we show that pre-DCs, but not other blood DC subsets, are susceptible to infection by HIV-1 in a Siglec-1–dependent manner. Siglec-1 mediates pre-DC infection of CCR5- and CXCR4-tropic strains. Infection of pre-DCs is further enhanced in the presence of HIV-2/SIVmac Vpx, indicating that Siglec-1 does not counteract restriction factors such as SAMHD1. Instead, Siglec-1 promotes attachment and fusion of viral particles. HIV-1–infected pre-DCs produce new infectious viral particles that accumulate in intracellular compartments reminiscent of the virus-containing compartment of macrophages. Pre-DC activation by toll-like receptor (TLR) ligands induces an antiviral state that inhibits HIV-1 fusion and infection, but Siglec-1 remains functional and mediates replication-independent transfer of HIV-1 to activated primary T lymphocytes. Altogether, Siglec-1–mediated susceptibility to HIV-1 infection of pre-DCs constitutes a unique functional feature that might represent a preferential relationship of this emerging cell type with viruses.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Constitutive Siglec-1 expression confers susceptibility to HIV-1 infection of human dendritic cell precursors

Ruffin

Gea‐Mallorquí

Brouiller

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…8,9 These macrophages present viral antigens to activate specific T cells, to induce activation, clonal proliferation, and subsequent killing of infected target cells through secretion of perforin, granzyme B, and interferon-γ etc. [10][11][12] Moreover, these activated T cells also egress from spleen and LNs into blood circulation and play immune surveillance roles. 13 Unfortunately, our previous work has shown that lymphocytopenia is prevalent in COVID-19 patients, especially in aged and critically ill cases, suggesting that the immune system from COVID-19 patients might be neutralized by infection.…”

Section: Introductionmentioning

confidence: 99%

The Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Directly Decimates Human Spleens and Lymph Nodes

chen

Feng

Diao³

et al. 2020

Preprint

333

325

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While lymphocytopenia is a common characteristic of patients infected by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the mechanisms responsible for this depletion are unclear. Through careful inspection of the spleens and lymph nodes (LNs) from six cases with postmortem examinations, we observed that SARS-CoV-2 could directly infect secondary lymphoid organs to induce cell death. Immunohistochemistry demonstrated ACE2 (angiotensin-converting enzyme 2), the potential receptor of SARS-CoV-2, expresses on tissue-resident CD169+ macrophages in spleens and LNs. Immunofluorescent staining confirmed that viral nucleocaspid protein (NP) can be found in ACE2+ cells, CD169+ macrophages, but not in CD3+ T cells or B220+ B cells in spleens and LNs. SARS-CoV-2 infection induces severe tissue damage including lymph follicle depletion, splenic nodule atrophy, histiocyte hyperplasia and lymphocyte reductions. Moreover, in situ TUNEL staining illustrated that viral infection leads to severe lymphocyte apoptosis, which might be mediated by viral antigens inducing Fas upregulation. Furthermore, SARS-CoV-2 also triggers macrophages to produce IL-6, a proinflammatory cytokine that directly promotes lymphocyte necrosis. Collectively, these results demonstrate that SARS-CoV-2 directly neutralizes human spleens and LNs through infecting tissue- resident CD169+ macrophages.

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“…The spleen has long been known as the main filter for blood and its microanatomic structure is optimized for intercepting circulating blood-borne pathogens. Splenic CD169+ macrophages, a subset of macrophages located in the splenic marginal zone, are on the front line of host defense to encounter blood borne pathogens (9)(10)(11). In addition to its defensive role, the human spleen also stores approximately one-third of the platelets that are generated by the bone marrow (12) and through retention of infused platelets the spleen can also affect platelet transfusion outcome (13).…”

Section: Introductionmentioning

confidence: 99%

Macrophage Depletion Mitigates Platelet Aggregate Formation in Splenic Marginal Zone and Alleviates LPS-Associated Thrombocytopenia in Rats

Liu

Ryan

et al. 2019

Front. Med.

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Sepsis is often accompanied with thrombocytopenia partly due to platelet sequestration in the lung and liver. The spleen can store up to one-third of circulating platelets and can also significantly affect platelet transfusion outcomes by accumulating platelets. However, in sepsis, it is not clear whether there are platelet changes in the spleen which could contribute to sepsis-associated thrombocytopenia and also influence platelet transfusion outcomes. By using confocal microscopy, we examined endogenous rat platelets and infused human platelets in the spleen of severe combined immune deficient Rag2 KO rats which were injected intraperitoneally with lipopolysaccharide (LPS). LPS-injected Rag2 KO rats developed sepsis as indicated by increased TNFa, IL-6, IL-1b, and IL-10 levels and thrombocytopenia. Large platelet aggregates were observed in the spleen with majority located in the marginal zone and closely associated with CD169+ macrophages. Depletion of macrophages by clodrosome resulted in reduction of LPS-induced cytokine generation and alleviated LPS-induced thrombocytopenia. Macrophage depletion also remarkedly diminished large platelet aggregate formation in the splenic marginal zone but had less effect on those in red pulp. Infusion of human platelets into LPS-injected rats failed to raise platelet counts in the peripheral blood. In LPS-injected rat spleen, human platelets interacted with aggregated rat platelets in the marginal zone. In contrast, human platelets infused into control rats were located outside of splenic marginal zone. This study provides morphological evidence of platelet aggregates in the splenic marginal zone in sepsis which can interact with infused platelets and thus can contribute to platelet infusion refractoriness in sepsis. It indicates that macrophages play an important role in LPS-associated thrombocytopenia. It also suggests that CD169+ macrophages support platelet aggregate formation in the splenic marginal zone.

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Functional CD169 on Macrophages Mediates Interaction with Dendritic Cells for CD8+ T Cell Cross-Priming

Cited by 106 publications

References 58 publications

Constitutive Siglec-1 expression confers susceptibility to HIV-1 infection of human dendritic cell precursors

Constitutive Siglec-1 expression confers susceptibility to HIV-1 infection of human dendritic cell precursors

The Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Directly Decimates Human Spleens and Lymph Nodes

Macrophage Depletion Mitigates Platelet Aggregate Formation in Splenic Marginal Zone and Alleviates LPS-Associated Thrombocytopenia in Rats

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