# Inflammasome activation and ehrlichial dissemination in tick vs needle transmission

> **NIH NIH R03** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2020 · $79,000

## Abstract

Abstract
Tick borne pathogens are important health concerns worldwide due to increasing numbers of diseases caused
by these microorganisms and also due to emergent/re-emerging diseases incidence. Many studies have
shown the intricacy of tick physiology and salivary components, which directly affect the success of disease
transmission. During attachment to the host for and feeding days or weeks, these arthropods induce significant
inflammation at the skin site of tick feeding as demonstrated in our and other researchers' studies.
Interestingly, proteins in saliva of different species of ticks have the properties of inducing many of the host
immune pathways, reducing or activating mechanisms of host defense. Depending on the pathogen carried by
ticks, the saliva of ticks could favor infection or host protection; however, the effect is usually to achieve
adaptation. Severe ehrlichial infection causes a dysregulation in the inflammatory host response that is
associated with tissue damage and increased pro-inflammatory cytokines. The inflammasome pathway is
implicated in modulation of the lethal imbalance. Sialostatins in tick saliva cause potential inhibition of host
NLRs and caspases; however, there is a lack of knowledge of the effect of tick attachment and feeding on
activation of inflammasome during transmission of ehrlichial pathogen. All studies evaluate highly reductionistic
individual cell responses to tick saliva, or the effects of a single salivary protein in the skin site of bacterial
inoculation, and so forth. We propose to evaluate the effects of a physiological mode of ehrlichial transmission
by its tick vector to understand the early host response involving the inflammasome pathway. Our central
hypothesis is that tick transmission of ehrlichiae modulates NLRP3 inflammasome pathway activation with
increased inflammatory response and recruitment of monocytes-macrophages to the infection site, favoring
bacterial dissemination and disease progression. In this proposal, we will characterize the dynamics of NLRP3-
caspase-1 inflammasome activation, monocyte-macrophage recruitment and bacterial dissemination induced
by ehrlichiae transmitted by ticks (Aim 1), and identify the role of the mode of infection on the modulation of
inflammasome activation during early ehrlichial disease (Aim 2). After accomplishing the aims of this project,
we will be able to determine the effects of EML transmitted by I. scapularis in activation of the inflammasome
complex and the importance of the mode of infection on this process. This study is timely as it addresses a
member of a genus of emerging pathogens and will offer new insights into disease pathogenesis and potential
for immunomodulatory therapy.

## Key facts

- **NIH application ID:** 9822947
- **Project number:** 5R03AI142406-02
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Bin Gong
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $79,000
- **Award type:** 5
- **Project period:** 2018-11-14 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9822947

## Citation

> US National Institutes of Health, RePORTER application 9822947, Inflammasome activation and ehrlichial dissemination in tick vs needle transmission (5R03AI142406-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9822947. Licensed CC0.

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