Site-Dependent Recruitment of Inflammatory Cells Determines the Effective Dose of Leishmania major

Ribeiro-Gomes, Flávia L.; Roma, Eric Henrique; Carneiro, Mariângela; Doria, Nicole; Sacks, David L.; Peters, Nathan C.

doi:10.1128/iai.01600-13

Cited by 66 publications

(98 citation statements)

References 48 publications

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“…Other studies have shown that L. major promastigotes trigger the release of TNF and IL-6, at least during the initial stages of infection (39,41,42). Furthermore, L. major promastigotes triggers the infiltration of inflammatory phagocytes shortly after inoculation (35)(36)(37). We expanded upon these findings by demonstrating that infected BMM secrete both of these cytokines and that release of TNF and IL-6 was dependent on the presence of GP63.…”

Section: Discussionmentioning

confidence: 70%

“…7A, 7B) levels in comparison with mice inoculated with Dgp63 parasites or to control mice. TNF and IL-6 are cytokines that act on a variety cells, including those of the endothelium (31), to induce chemokine release and adhesion molecules and thence inflammatory phagocyte accrual to the inflammation site (31,33,34).Taken together with the fact that L. major promastigotes induce inflammatory phagocyte recruitment to the infection site (35,36), we investigated whether GP63 played a role in this phenomenon. Four hours postinoculation, we observed a GP63-dependent increase in CD11b + myeloid cell recruitment (Fig.…”

Section: Gp63-expressing Promastigotes Elicit Increased Tnf and Il-6 mentioning

confidence: 99%

“…Inoculation of L. major promastigotes has been shown to be followed by the infiltration of neutrophils and inflammatory monocytes. Both of these cell types are infection targets and important for the establishment of infection (35)(36)(37). Syts are regulators of SNARE complex activity and play a role in cytokine release.…”

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confidence: 99%

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Leishmania Promastigotes Induce Cytokine Secretion in Macrophages through the Degradation of Synaptotagmin XI

Duque

Fukuda

Turco

et al. 2014

The Journal of Immunology

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Synaptotagmins (Syts) are type-I membrane proteins that regulate vesicle docking and fusion in processes such as exocytosis and phagocytosis. We recently discovered that Syt XI is a recycling endosome- and lysosome-associated protein that negatively regulates the secretion of TNF and IL-6. In this study, we show that Syt XI is directly degraded by the zinc metalloprotease GP63 and excluded from Leishmania parasitophorous vacuoles by the promastigotes surface glycolipid lipophosphoglycan. Infected macrophages were found to release TNF and IL-6 in a GP63-dependent manner. To demonstrate that cytokine release was dependent on GP63-mediated degradation of Syt XI, small interfering RNA-mediated knockdown of Syt XI before infection revealed that the effects of small interfering RNA knockdown and GP63 degradation were not cumulative. In mice, i.p. injection of GP63-expressing parasites led to an increase in TNF and IL-6 secretion and to an augmented influx of neutrophils and inflammatory monocytes to the inoculation site. Both of these cell types have been shown to be infection targets and aid in the establishment of infection. In sum, our data revealed that GP63 induces proinflammatory cytokine release and increases infiltration of inflammatory phagocytes. This study provides new insight on how Leishmania exploits the immune response to establish infection.

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Section: Discussionmentioning

confidence: 70%

Section: Gp63-expressing Promastigotes Elicit Increased Tnf and Il-6 mentioning

confidence: 99%

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Leishmania Promastigotes Induce Cytokine Secretion in Macrophages through the Degradation of Synaptotagmin XI

Duque

Fukuda

Turco

et al. 2014

The Journal of Immunology

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“…Currently, there are several antibodies considered useful for neutrophil depletion; however, none of them depleted neutrophils completely. The antibodies NIMP-R14 and RB6-8C5 have a high degree of specificity for murine Ly-6G and Ly-6C, and consequently depleted not only neutrophils but also monocytes and macrophages [42][43][44] . On the other hand, the 1A8 antibody recognizes only Ly6G, which results in an adequate and more specific depletion of neutrophils, but less efficient than antibodies used in previous experiments 43,44 .…”

Section: Discussionmentioning

confidence: 99%

“…The antibodies NIMP-R14 and RB6-8C5 have a high degree of specificity for murine Ly-6G and Ly-6C, and consequently depleted not only neutrophils but also monocytes and macrophages [42][43][44] . On the other hand, the 1A8 antibody recognizes only Ly6G, which results in an adequate and more specific depletion of neutrophils, but less efficient than antibodies used in previous experiments 43,44 . Therefore, differences in the specific hapten and/or neutrophil antibodies used in a particular experiment may yield different populations of depleted cells, leading to disparate results including IFN-γ production.…”

Section: Discussionmentioning

confidence: 99%

Aquaporin-9-expressing neutrophils are required for the establishment of contact hypersensitivity

Moniaga

Hara‐Chikuma

2016

Journal of Dermatological Science

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1Aquaporin-9 (AQP9), a water/glycerol channel protein, is expressed in several immune cells including neutrophils; however, its role in immune response remains unknown. Here we show the involvement of AQP9 in hapten-induced contact hypersensitivity (CHS), as a murine model of skin allergic contact dermatitis, using AQP9 knockout (AQP9 −/− ) mice. First, the CHS response to hapten dinitrofluorobenzene (DNFB) was impaired in AQP9 −/− mice compared with wild-type (WT) mice. Adoptive transfer of sensitized AQP9 −/− draining lymph node (dLN) cells into WT recipients resulted in a reduced CHS response, indicating impaired sensitization in AQP9 −/− mice. Second, administration of WT neutrophils into AQP9 −/− mice during sensitization rescued the impaired CHS response. Neutrophil recruitment to dLNs upon hapten application was attenuated by AQP9 deficiency. Coincidentally, AQP9 −/− neutrophils showed a reduced CC-chemokine receptor 7 (CCR7) ligand-induced migration efficacy, which was attributed to the attenuated recruitment of neutrophils to dLNs. Furthermore, we found that neutrophil deficiency, observed in AQP9 −/− or neutrophildepleted mice, decreased IL-17A production by dLN cells, which might be responsible for T cell activation during a subsequent CHS response. Taken together, these findings suggest that AQP9 is required for the development of sensitization during cutaneous acquired immune responses via regulating neutrophil function.Allergic contact dermatitis (ACD) is one of the most prevalent skin diseases consisting of sensitization and elicitation phases 1,2 . Advanced studies of hapten-induced contact hypersensitivity (CHS) as a murine model of ACD have expanded our understanding of the mechanism of allergic reactions occurring in the skin, especially the specific roles of a variety of immune cells. During the sensitization phase, hapten-bearing cutaneous dendritic cells (DCs) migrate into skin draining lymph nodes (dLNs), where the presentation of antigens to naïve T cells and subsequent T cell priming occur. During the elicitation phase, re-exposure to cognate hapten results in the recruitment of antigen-specific T cells to the site of allergen challenge and T cell-mediated tissue damage 2 . Increasing evidence shows that several subsets of immune cells, including various types of T cells (Th1, Th17, regulatory, and natural killer), DCs (dermal DCs and Langerhans cells), and mast cells, work synergistically in the skin and its dLNs to exert antigen presentation and T cell activation during the development of sensitization in CHS [3][4][5][6][7] . Neutrophils have long been considered as the final effector cells of an acute inflammatory response. On the other hand, accumulating evidence has extended the function of neutrophils to include activation and regulation during innate and adaptive immune responses 8,9 . Several studies have focused on the

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Animal Models for the Analysis of Immune Responses to Leishmaniasis

Sacks

Melby

2015

CP in Immunology

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Site-Dependent Recruitment of Inflammatory Cells Determines the Effective Dose of Leishmania major

Cited by 66 publications

References 48 publications

Leishmania Promastigotes Induce Cytokine Secretion in Macrophages through the Degradation of Synaptotagmin XI

Leishmania Promastigotes Induce Cytokine Secretion in Macrophages through the Degradation of Synaptotagmin XI

Aquaporin-9-expressing neutrophils are required for the establishment of contact hypersensitivity

Animal Models for the Analysis of Immune Responses to Leishmaniasis

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