The Origin and Maturity of Dendritic Cells Determine the Pattern of Sphingosine 1-Phosphate Receptors Expressed and Required for Efficient Migration

Rathinasamy, Anchana; Czeloth, Niklas; Pabst, Oliver; Förster, Reinhold; Bernhardt, Günter

doi:10.4049/jimmunol.1000568

Cited by 60 publications

(61 citation statements)

References 43 publications

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“…Treatment with FTY720 restricts the migration of circulating cells, so a stable population of Trm cells in treated mice demonstrates that these cells are neither replenished by, nor lost to, circulating populations 15, 17, 40. However, FTY720 may also inhibit egress of cells from peripheral tissues to draining lymph nodes and/or reduce cell survival 35, 41, 42, 43. Despite these potential caveats, results from FTY720‐treated animals reflect those from more elegant parabiosis experiments that demonstrate that Trm cells are a distinct population neither leaving the tissue nor being replenished by circulating cells 17, 30…”

Section: Memory Cd4 T‐cells Are Found Throughout the Bodymentioning

confidence: 99%

The roles of resident, central and effector memory CD4 T‐cells in protective immunity following infection or vaccination

2018

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SummaryImmunological memory provides rapid protection to pathogens previously encountered through infection or vaccination. CD4 T‐cells play a central role in all adaptive immune responses. Vaccines must, therefore, activate CD4 T‐cells if they are to generate protective immunity. For many diseases, we do not have effective vaccines. These include human immunodeficiency virus (HIV), tuberculosis and malaria, which are responsible for many millions of deaths each year across the globe. CD4 T‐cells play many different roles during the immune response coordinating the actions of many other cells. In order to harness the diverse protective effects of memory CD4 T‐cells, we need to understand how memory CD4 T‐cells are generated and how they protect the host. Here we review recent findings on the location of different subsets of memory CD4 T‐cells that are found in peripheral tissues (tissue resident memory T‐cells) and in the circulation (central and effector memory T‐cells). We discuss the generation of these cells, and the evidence that demonstrates how they provide immune protection in animal and human challenge models.

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Section: Memory Cd4 T‐cells Are Found Throughout the Bodymentioning

confidence: 99%

The roles of resident, central and effector memory CD4 T‐cells in protective immunity following infection or vaccination

2018

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“…In vivo, NK cell trafficking is dependent upon S1P (12); and similar to lymphocytes, FTY720 treatment restricts NK cell egress from lymph nodes and bone marrow (13). Additionally, migration of in vitro generated, mature S1P 1 2/2 or S1P 3 2/2 dendritic cells is defective following injection into mice (14). The role of S1P receptors on monocytes in vivo is less clear.…”

mentioning

confidence: 99%

Circulating Monocytes Are Reduced by Sphingosine-1-Phosphate Receptor Modulators Independently of S1P3

Lewis

Haxhinasto

Anderson

et al. 2013

The Journal of Immunology

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Sphingosine-1-phosphate (S1P) receptors are critical for lymphocyte egress from secondary lymphoid organs, and S1P receptor modulators suppress lymphocyte circulation. However, the role of S1P receptors on monocytes is less clear. To elucidate this, we systematically evaluated monocytes in rats and mice, both in naive and inflammatory conditions, with S1P receptor modulators FTY720 and BAF312. We demonstrate that S1P receptor modulators reduce circulating monocytes in a similar time course as lymphocytes. Furthermore, total monocyte numbers were increased in the spleen and bone marrow, suggesting that S1P receptor modulation restricts egress from hematopoietic organs. Monocytes treated ex vivo with FTY720 had reduced CD40 expression and TNF-α production, suggesting a direct effect on monocyte activation. Similar reductions in protein expression and cytokine production were also found in vivo. Suppression of experimental autoimmune encephalomyelitis in mice and rats by FTY720 correlated with reduced numbers of lymphocytes and monocytes. These effects on monocytes were independent of S1P3, as treatment with BAF312, a S1P1,4,5 modulator, led to similar results. These data reveal a novel role for S1P receptors on monocytes and offer additional insights on the mechanism of action of S1P receptor modulators in disease.

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“…1), which was the earliest time point of evaluation in this study, and continued for the entire 60-day period of the mouse survival study. Since S1P is known to contribute to immune cell migration (29,38,39) and phagocytosis (21), these results indicate a sustainable immune response against C. neoformans ⌬gcs1 infection throughout the infection.…”

Section: Discussionmentioning

confidence: 79%

“…Since SK1 and S1P are regulators of host immunity (27)(28)(29)(30)(31) and antimicrobial activity (2,20), we wondered whether the SK1-S1P pathway is stimulated by C. neoformans infection and if there is a difference in the stimulation of this pathway between wild-type (WT) C. neoformans strain H99 (which causes 100% mortality in mouse models) and C. neofor-mans ⌬gcs1 (which can be contained in the lungs of mice without causing mortality) (9).…”

Section: Resultsmentioning

confidence: 99%

The Granuloma Response Controlling Cryptococcosis in Mice Depends on the Sphingosine Kinase 1–Sphingosine 1-Phosphate Pathway

et al. 2015

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cCryptococcus neoformans is a fungal pathogen that causes pulmonary infections, which may progress into life-threatening meningitis. In commonly used mouse models of C. neoformans infections, fungal cells are not contained in the lungs, resulting in dissemination to the brain. We have previously reported the generation of an engineered C. neoformans strain (C. neoformans ⌬gcs1) which can be contained in lung granulomas in the mouse model and have shown that granuloma formation is dependent upon the enzyme sphingosine kinase 1 (SK1) and its product, sphingosine 1-phosphate (S1P). In this study, we have used four mouse models, CBA/J and C57BL6/J (both immunocompetent), Tg26 (an isogenic strain of strain CBA/J lacking T and NK cells), and SK ؊/؊ (an isogenic strain of strain C57BL6/J lacking SK1), to investigate how the granulomatous response and SK1-S1P pathway are interrelated during C. neoformans infections. S1P and monocyte chemotactic protein-1 (MCP-1) levels were significantly elevated in the bronchoalveolar lavage fluid of all mice infected with C. neoformans ⌬gcs1 but not in mice infected with the C. neoformans wild type. SK1؊/؊ mice did not show elevated levels of S1P or MCP-1. Primary neutrophils isolated from SK1 ؊/؊ mice showed impaired antifungal activity that could be restored by the addition of extracellular S1P. In addition, high levels of tumor necrosis factor alpha were found in the mice infected with C. neoformans ⌬gcs1 in comparison to the levels found in mice infected with the C. neoformans wild type, and their levels were also dependent on the SK1-S1P pathway. Taken together, these results suggest that the SK1-S1P pathway promotes host defense against C. neoformans infections by regulating cytokine levels, promoting extracellular killing by phagocytes, and generating a granulomatous response. C ryptococcosis is a serious fungal infection in immunocompromised hosts that results in deadly meningitis once fungi disseminate to the central nervous system (CNS) (1-3). Cryptococcus neoformans is a common environmental fungus, and exposure is thought to be extremely prevalent but rarely progresses to disease in healthy individuals (4-6). Most human hosts are able to combat and contain C. neoformans in the lungs to prevent spread to the CNS. A successful immune response results in the killing of C. neoformans and the formation of a granuloma in the lungs, which is thought to prevent C. neoformans from accessing the vasculature and causing infection of the CNS. Under conditions of immune suppression, this response does not occur successfully and C. neoformans survives within macrophages, which are thought to transport C. neoformans across the blood-brain barrier and lead to life-threatening meningitis (3, 5). Although significant work has been done to elucidate the role of the host defense during early pulmonary infection, much work regarding the development of a granuloma in response to C. neoformans remains to be done (7,8).Despite the induction of proinflammatory cytokines in commonly used mouse mode...

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The Origin and Maturity of Dendritic Cells Determine the Pattern of Sphingosine 1-Phosphate Receptors Expressed and Required for Efficient Migration

Abstract: Material

Cited by 60 publications

References 43 publications

The roles of resident, central and effector memory CD4 T‐cells in protective immunity following infection or vaccination

The roles of resident, central and effector memory CD4 T‐cells in protective immunity following infection or vaccination

Circulating Monocytes Are Reduced by Sphingosine-1-Phosphate Receptor Modulators Independently of S1P3

The Granuloma Response Controlling Cryptococcosis in Mice Depends on the Sphingosine Kinase 1–Sphingosine 1-Phosphate Pathway

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