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Amblyomma americanum ticks utilizes countervailing pro and anti-inflammatory proteins to evade host defense.
- Source :
-
PLoS pathogens [PLoS Pathog] 2019 Nov 22; Vol. 15 (11), pp. e1008128. Date of Electronic Publication: 2019 Nov 22 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- Feeding and transmission of tick-borne disease (TBD) agents by ticks are facilitated by tick saliva proteins (TSP). Thus, defining functional roles of TSPs in tick evasion is expected to reveal potential targets in tick-antigen based vaccines to prevent TBD infections. This study describes two types of Amblyomma americanum TSPs: those that are similar to LPS activate macrophage (MΦ) to express pro-inflammation (PI) markers and another set that suppresses PI marker expression by activated MΦ. We show that similar to LPS, three recombinant (r) A. americanum insulin-like growth factor binding-related proteins (rAamIGFBP-rP1, rAamIGFBP-rP6S, and rAamIGFBP-rP6L), hereafter designated as PI-rTSPs, stimulated both PBMC -derived MΦ and mice RAW 267.4 MΦ to express PI co-stimulatory markers, CD40, CD80, and CD86 and cytokines, TNFα, IL-1, and IL-6. In contrast, two A. americanum tick saliva serine protease inhibitors (serpins), AAS27 and AAS41, hereafter designated as anti-inflammatory (AI) rTSPs, on their own did not affect MΦ function or suppress expression of PI markers, but enhanced expression of AI cytokines (IL-10 and TGFβ) in MΦ that were pre-activated by LPS or PI-rTSPs. Mice paw edema test demonstrated that in vitro validated PI- and AI-rTSPs are functional in vivo since injection of HEK293-expressed PI-rTSPs (individually or as a cocktail) induced edema comparable to carrageenan-induced edema and was characterized by upregulation of CD40, CD80, CD86, TNF-α, IL-1, IL-6, and chemokines: CXCL1, CCL2, CCL3, CCL5, and CCL11, whereas the AI-rTSPs (individually and cocktail) were suppressive. We propose that the tick may utilize countervailing PI and AI TSPs to regulate evasion of host immune defenses whereby TSPs such as rAamIGFBP-rPs activate host immune cells and proteins such as AAS27 and AAS41 suppress the activated immune cells.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Animals
Arthropod Proteins genetics
Female
HEK293 Cells
Host-Parasite Interactions
Humans
Macrophages immunology
Macrophages metabolism
Mice
Mice, Inbred BALB C
Tick Infestations immunology
Tick Infestations metabolism
Anti-Inflammatory Agents metabolism
Arthropod Proteins metabolism
Inflammation Mediators metabolism
Macrophages parasitology
Saliva metabolism
Tick Infestations parasitology
Ticks pathogenicity
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7374
- Volume :
- 15
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- PLoS pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 31756216
- Full Text :
- https://doi.org/10.1371/journal.ppat.1008128