Immunosuppressive effects of Amblyomma cajennense tick saliva on murine bone marrow-derived dendritic cells View Full Text


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Article Info

DATE

2015-01-14

AUTHORS

Tamires Marielem Carvalho-Costa, Maria Tays Mendes, Marcos Vinicius da Silva, Thiago Alvares da Costa, Monique Gomes Salles Tiburcio, Ana Carolina Borella Marfil Anhê, Virmondes Rodrigues, Carlo Jose Freire Oliveira

ABSTRACT

BACKGROUND: Dendritic cells (DCs) are professional antigen-presenting cells with vital roles in the activation of host immunity. Ticks are bloodsucking arthropods that secrete bioactive compounds with immunomodulatory properties via their saliva. It is known that some tick species modulate the biology of DCs with different intensities; however, studies on Amblyomma cajennense, the Cayenne tick, have not yet been performed, although this species is considered one of the most capable of modulating immune responses of different hosts. METHODS: Engorged female ticks were stimulated with dopamine to induce salivation, and saliva was pooled. The effects of tick saliva on the biology of dendritic cells were assessed by examining DC differentiation, maturation, migration, cellular viability, cytokine production and expression of surface markers by flow cytometry and ELISA. Competitive enzyme immunoassays (EIA) were used to measure saliva prostaglandin-E2 (PGE2). Statistical significance was determined by ANOVA followed by Tukey's post-test or by the Kruskal-Wallis test with the Dunns post-test. RESULTS: In this work, we demonstrated that the presence of A. cajennense saliva to bone marrow cultures inhibit DC differentiation. This inhibition was not accompanied by inhibition or induction of stimulatory and co-stimulatory molecules such as MHC-II, CD40, CD80 or CD86. Immature and mature DCs that were pre-exposed to saliva showed reduced migration toward the chemokines RANTES and MIP-3β. This inhibition was associated to a reduced expression of CCR5 (the receptor for RANTES) or CCR7 (the receptor for MIP-3β) induced by the presence of saliva in the cultures. Tick saliva also inhibited IL-12p40, IL-6 and TNF-α in a concentration-dependent manner while potentiating IL-10 cytokine production by DCs stimulated with Toll-like receptor-4 ligand. Additionally, A. cajennense tick saliva inhibited the expression of CD40 and CD86 in mature DCs while potentiating the expression of PD-L1. PGE2 was detected as one of the constituents of saliva at a concentration of ~ 80 ng/ml, and we believe that most of the results reported herein are due to the presence of PGE2. CONCLUSIONS: These results help to understand the tick-host interaction and demonstrate that A. cajennense ticks appear to have mechanisms for modulating host immune cells, including DCs. More... »

PAGES

22

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s13071-015-0634-7

DOI

http://dx.doi.org/10.1186/s13071-015-0634-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1040041617

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25586117


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30 schema:description BACKGROUND: Dendritic cells (DCs) are professional antigen-presenting cells with vital roles in the activation of host immunity. Ticks are bloodsucking arthropods that secrete bioactive compounds with immunomodulatory properties via their saliva. It is known that some tick species modulate the biology of DCs with different intensities; however, studies on Amblyomma cajennense, the Cayenne tick, have not yet been performed, although this species is considered one of the most capable of modulating immune responses of different hosts. METHODS: Engorged female ticks were stimulated with dopamine to induce salivation, and saliva was pooled. The effects of tick saliva on the biology of dendritic cells were assessed by examining DC differentiation, maturation, migration, cellular viability, cytokine production and expression of surface markers by flow cytometry and ELISA. Competitive enzyme immunoassays (EIA) were used to measure saliva prostaglandin-E2 (PGE2). Statistical significance was determined by ANOVA followed by Tukey's post-test or by the Kruskal-Wallis test with the Dunns post-test. RESULTS: In this work, we demonstrated that the presence of A. cajennense saliva to bone marrow cultures inhibit DC differentiation. This inhibition was not accompanied by inhibition or induction of stimulatory and co-stimulatory molecules such as MHC-II, CD40, CD80 or CD86. Immature and mature DCs that were pre-exposed to saliva showed reduced migration toward the chemokines RANTES and MIP-3β. This inhibition was associated to a reduced expression of CCR5 (the receptor for RANTES) or CCR7 (the receptor for MIP-3β) induced by the presence of saliva in the cultures. Tick saliva also inhibited IL-12p40, IL-6 and TNF-α in a concentration-dependent manner while potentiating IL-10 cytokine production by DCs stimulated with Toll-like receptor-4 ligand. Additionally, A. cajennense tick saliva inhibited the expression of CD40 and CD86 in mature DCs while potentiating the expression of PD-L1. PGE2 was detected as one of the constituents of saliva at a concentration of ~ 80 ng/ml, and we believe that most of the results reported herein are due to the presence of PGE2. CONCLUSIONS: These results help to understand the tick-host interaction and demonstrate that A. cajennense ticks appear to have mechanisms for modulating host immune cells, including DCs.
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37 schema:keywords ANOVA
38 Amblyomma cajennense
39 CCR5
40 CCR7
41 CD40
42 CD80
43 CD86
44 Cayenne tick
45 DC differentiation
46 Dunn
47 ELISA
48 IL-10 cytokine production
49 IL-12p40
50 IL-6
51 Kruskal-Wallis test
52 MHC
53 MIP-3β
54 PD-L1
55 RANTES
56 TNF
57 Toll-like receptor-4 ligand
58 Tukey
59 activation
60 antigen-presenting cells
61 arthropods
62 bioactive compounds
63 biology
64 biology of DCs
65 bone marrow cultures
66 bone marrow-derived dendritic cells
67 cajennense
68 cajennense saliva
69 cajennense tick saliva
70 cajennense ticks
71 cells
72 cellular viability
73 chemokine RANTES
74 co-stimulatory molecules
75 competitive enzyme immunoassay
76 compounds
77 concentration
78 concentration-dependent manner
79 constituents
80 constituents of saliva
81 culture
82 cytokine production
83 cytometry
84 dendritic cells
85 different hosts
86 different intensities
87 differentiation
88 dopamine
89 effect
90 enzyme immunoassay
91 expression
92 expression of CD40
93 female ticks
94 flow cytometry
95 host
96 host immune cells
97 host immunity
98 immune cells
99 immune response
100 immunity
101 immunoassay
102 immunomodulatory properties
103 immunosuppressive effects
104 induction
105 induction of stimulatory
106 inhibition
107 intensity
108 interaction
109 ligands
110 manner
111 markers
112 marrow cultures
113 marrow-derived dendritic cells
114 maturation
115 mature dendritic cells
116 mechanism
117 migration
118 molecules
119 murine bone marrow-derived dendritic cells
120 presence
121 presence of PGE2
122 presence of saliva
123 production
124 professional antigen-presenting cells
125 properties
126 prostaglandin-E2
127 receptor-4 ligand
128 reduced expression
129 reduced migration
130 response
131 results
132 role
133 saliva
134 saliva prostaglandin-E2
135 salivation
136 significance
137 species
138 statistical significance
139 stimulatory
140 study
141 surface markers
142 test
143 tick saliva
144 tick species
145 tick-host interactions
146 ticks
147 viability
148 vital role
149 work
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