Immunomodulatory Effects of Amblyomma variegatum Saliva on Bovine Cells: Characterization of Cellular Responses and Identification of Molecular Determinants

Rodrigues, Valérie; Fernandez, Bernard; Vercoutere, Arthur; Chamayou, Léo; Andersen, Alexandre; Vigy, Oana; Demettre, Edith; Séveno, Martial; Aprelon, Rosalie; Giraud-Girard, Ken; Stachurski, Frédéric; Loire, Étienne; Vachiéry, Nathalie; Holzmüller, Philippe

doi:10.3389/fcimb.2017.00521

Cited by 16 publications

(9 citation statements)

References 87 publications

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“…These factors have been reported to play a role in the activation and/or recruitment of multiple resident and infiltrating cell types at the tick bite site, including macrophages, mast cells, dendritic cells, endothelial cells, keratinocytes, and lymphocytes, as well as in the polarization of an initial Th1 helper response towards a Th2 orientation, considered to be more favourable to tick blood-feeding [29]. Here we showed that IrSPI inhibits mitogen-induced proliferation of murine CD4 + T cells, as has been reported for saliva of not only I. ricinus [48], but also several other tick species including D. andersoni [49], A. variegatum [50], and I. dammini [51]. It is noteworthy that in our study, IrSPI inhibited secretion of IL-9, which promotes the proliferation of CD4 + rather than CD8 + T cells [52].…”

Section: Discussionsupporting

confidence: 83%

The Immunomodulatory Effect of IrSPI, a Tick Salivary Gland Serine Protease Inhibitor Involved in Ixodes ricinus Tick Feeding

et al. 2019

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Ticks are the most important vectors of pathogens affecting both domestic and wild animals worldwide. Hard tick feeding is a slow process—taking up to several days—and necessitates extended control over the host response. The success of the feeding process depends upon injection of tick saliva, which not only controls host hemostasis and wound healing, but also subverts the host immune response to avoid tick rejection that creates a favorable niche for the survival and propagation of diverse tick-borne pathogens. Here, we report on the molecular and biochemical features and functions of an Ixodes ricinus serine protease inhibitor (IrSPI). We characterize IrSPI as a Kunitz elastase inhibitor that is overexpressed in several tick organs—especially salivary glands—during blood-feeding. We also demonstrated that when IrSPI is injected into the host through saliva, it had no impact on tissue factor pathway-induced coagulation, fibrinolysis, endothelial cell angiogenesis or apoptosis, but the protein exhibits immunomodulatory activity. In particular, IrSPI represses proliferation of CD4+ T lymphocytes and proinflammatory cytokine secretion from both splenocytes and macrophages. Our study contributes valuable knowledge to tick-host interactions and provides insights that could be further exploited to design anti-tick vaccines targeting this immunomodulator implicated in I. ricinus feeding.

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Section: Discussionsupporting

confidence: 83%

The Immunomodulatory Effect of IrSPI, a Tick Salivary Gland Serine Protease Inhibitor Involved in Ixodes ricinus Tick Feeding

et al. 2019

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“…These factors have been reported to play a role in the activation and/or recruitment of multiple resident and infiltrating cell types at the tick bite site, including macrophages, mast cells, dendritic cells, endothelial cells, keratinocytes, and lymphocytes, as well as in the polarisation of an initial Th1 helper response towards a Th2 orientation, considered to be more favourable to tick blood feeding [11]. Here we showed that IrSPI inhibits mitogen-induced proliferation of murine CD4 + T cells, as has been reported for saliva of not only I. ricinus [29], but also several other tick species including D. andersoni [30], A. variegatum [31], and I. dammini [32]. It is noteworthy that in our study, IrSPI inhibited secretion of IL-9, which promotes the proliferation of CD4 + rather than CD8 + T cells [33].…”

Section: Discussionsupporting

confidence: 80%

The immunomodulatory effect of IrSPI, a tick salivary gland serine protease inhibitor involved inIxodes ricinustick feeding

Blisnick

Šimo

Grillon

et al. 2019

Preprint

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30Ticks are strict hematophagous arthropods and are the most important vectors of pathogens 31 affecting both domestic and wild animals worldwide. Moreover, they are second only to mosquitoes as 32 vectors of human pathogens. Hard tick feeding is a slow process-taking up to several days for repletion 33 prior to detachment-and necessitates extended control over the host response. The success of the 34 feeding process depends upon injection of saliva by tick, which not only controls host haemostasis and 35 wound healing, but also subverts the host immune response to avoid tick rejection during this long-36 lasting process. In turn, the manipulation of the host immune response creates a favourable niche for the 37 survival and propagation of diverse tick-borne pathogens transmitted during feeding. Here, we report 38 on the molecular and biochemical features and functions of IrSPI, an Ixodes ricinus salivary serine 39 protease inhibitor involved in blood meal acquisition. Our results show that IrSPI harbours the typical 40 conformational fold of Kunitz type I serine protease inhibitors and that it functionally inhibits the 41 elastase and, to a lesser extent, chymotrypsin. We also show that IrSPI is injected into the host during 42 feeding. Crucially, we found that IrSPI has no impact on tissue factor pathway-induced coagulation, 43 fibrinolysis, apoptosis, or angiogenesis, but a strong effect on immune cells. IrSPI affects antigen-44 presenting macrophages by hampering IL-5 production. In addition, IrSPI represses proliferation of 45 mitogen-stimulated CD4 + cells. The inhibition of T cell proliferation was associated with marked 46 reductions in pro-inflammatory cytokine secretion. Our study contributes valuable knowledge to tick-47 host interactions and provides insights that could be further exploited to design anti-tick vaccines 48 targeting this immunomodulator implicated in successful I. ricinus tick feeding. 50Author summary 51 Ticks are the most important vector influencing both human and animal health in Europe, where 52 Ixodes ricinus is the most abundant tick species. Ticks feed on animal or human blood for an extended 53 period, during which their saliva allows both feeding and pathogen transmission by interfering with 54 native host responses. A better understanding of tick-host-pathogen interactions is central to the 55 discovery of improved control methods. Within this context, we previously identified IrSPI as an I.3 56 ricinus salivary molecule implicated in both tick feeding and bacterial transmission. This serine protease 57 inhibitor was almost characterised as an elastase inhibitor, and here, we show IrSPI overexpression in 58 several tick organs-especially salivary glands-during blood feeding. We demonstrate that IrSPI is 59 injected into the host through saliva, and despite having no impact on endothelial cell angiogenesis or 60 apoptosis during blood feeding, we report an immunomodulatory role, whereby CD4 + T lymphocyte 61 proliferation is repressed and where the cytokine secretion pattern ...

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“…These genes are highly polymorphic and are less defined in species such as cattle. Several tick immunological studies have demonstrated that different MHC2 classes are responsible for tick resistance or susceptibility [ 115 , 116 ]; however, these findings have not been used to inform vaccine research directly. Some researchers have tried to predict B cell and/or T cell binding epitopes in putative tick vaccine candidates (reviewed by Lew-Tabor and Rodriguez Valle [ 6 , 117 ]); however, the tools for these bioinformatics predictions for use in non-human hosts have yet to be developed.…”

Section: Potential Constraints Toward Cocktail Vaccine Efficacymentioning

confidence: 99%

Cocktail Anti-Tick Vaccines: The Unforeseen Constraints and Approaches toward Enhanced Efficacies

Ndawula

Lew-Tabor

2020

Vaccines

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Ticks are second to mosquitoes as vectors of disease. Ticks affect livestock industries in Asia, Africa and Australia at ~$1.13 billion USD per annum. For instance, 80% of the global cattle population is at risk of infestation by the Rhipicephalus microplus species-complex, which in 2016 was estimated to cause $22–30 billion USD annual losses. Although the management of tick populations mainly relies on the application of acaricides, this raises concerns due to tick resistance and accumulation of chemical residues in milk, meat, and the environment. To counteract acaricide-resistant tick populations, immunological tick control is regarded among the most promising sustainable strategies. Indeed, immense efforts have been devoted toward identifying tick vaccine antigens. Until now, Bm86-based vaccines have been the most effective under field conditions, but they have shown mixed success worldwide. Currently, of the two Bm86 vaccines commercialized in the 1990s (GavacTM in Cuba and TickGARDPLUSTM in Australia), only GavacTM is available. There is thus growing consensus that combining antigens could broaden the protection range and enhance the efficacies of tick vaccines. Yet, the anticipated outcomes have not been achieved under field conditions. Therefore, this review demystifies the potential limitations and proposes ways of sustaining enhanced cocktail tick vaccine efficacy.

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Immunomodulatory Effects of Amblyomma variegatum Saliva on Bovine Cells: Characterization of Cellular Responses and Identification of Molecular Determinants

Cited by 16 publications

References 87 publications

The Immunomodulatory Effect of IrSPI, a Tick Salivary Gland Serine Protease Inhibitor Involved in Ixodes ricinus Tick Feeding

The Immunomodulatory Effect of IrSPI, a Tick Salivary Gland Serine Protease Inhibitor Involved in Ixodes ricinus Tick Feeding

The immunomodulatory effect of IrSPI, a tick salivary gland serine protease inhibitor involved inIxodes ricinustick feeding

Cocktail Anti-Tick Vaccines: The Unforeseen Constraints and Approaches toward Enhanced Efficacies

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