Amblyomma americanum ticks utilizes countervailing pro and anti-inflammatory proteins to evade host defense.

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.

• Authors: Mariam Bakshi, Tae Kwon Kim, Lindsay Porter, Waithaka Mwangi, Albert Mulenga
• Journal: PLoS pathogens (PLoS Pathog) Vol. 15 Issue 11 Pg. e1008128 (11 2019) ISSN: 1553-7374 [Electronic] United States
• PMID: 31756216 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Arthropod Proteins
• Inflammation Mediators

Topics

• Animals
• Anti-Inflammatory Agents (metabolism)
• Arthropod Proteins (genetics, metabolism)
• Female
• HEK293 Cells
• Host-Parasite Interactions
• Humans
• Inflammation Mediators (metabolism)
• Macrophages (immunology, metabolism, parasitology)
• Mice
• Mice, Inbred BALB C
• Saliva (metabolism)
• Tick Infestations (immunology, metabolism, parasitology)
• Ticks (pathogenicity)