# Mechanisms of persistence in Trypanosoma cruzi infection

> **NIH NIH R01** · UNIVERSITY OF GEORGIA · 2020 · $375,000

## Abstract

Abstract
The premise of this proposal is that the very early events in immune recognition of a pathogen play a crucial role in its
ultimate control and tell us a great deal about the potential for cure or prevention of an infection (via vaccination, for
example). Over the past ~30 years we have developed an understanding of the various mechanisms that contribute to
the ability of hosts to control T. cruzi infection. We also know that in the vast majority of cases, T. cruzi is very effectively
controlled but it is extremely rare for the infection to be totally cleared, thus resulting in clinical disease known as Chagas
disease. What remains largely unknown is why the otherwise highly effective immune response generated during T.
cruzi infection so often fails to completely resolve the infection. The hypothesis that underlies the work proposed in this
application is that the eventual success of T. cruzi is a consequence of the parasite’s ability to invade host cells with
minimal triggering of host pattern recognition receptors (PRR) and then elicit responses that are largely focused on highly
variant parasite proteins. The combination of these two factors delays and diverts the adaptive immune responses not
only at the very beginning of the infection but also at new infection sites within the infected host throughout the
infection. The consequence of this situation is the persistence of the infection in most hosts and the susceptibility to
reinfection of “immune”, previously infected, or currently infected hosts. In this project we further investigate the
mechanisms of detection by and evasion of both innate and adaptive immune responses in T. cruzi infection. We will
also manipulate the host:parasite interaction by modifying the parasite targets of potential innate and adaptive immune
responses and observing the consequences of these manipulations on the ability of T. cruzi to persist in a natural host
and to induce sterile protection. The results of these studies will provide insights on how the chronic persistence of T.
cruzi can be prevented, and thus approaches for immunotherapies in persistently infected subjects. These studies will
also inform on the potential for development of prophylactic vaccines to prevent T. cruzi infection.

## Key facts

- **NIH application ID:** 9979735
- **Project number:** 5R01AI124692-05
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Rick L Tarleton
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $375,000
- **Award type:** 5
- **Project period:** 2016-09-23 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979735

## Citation

> US National Institutes of Health, RePORTER application 9979735, Mechanisms of persistence in Trypanosoma cruzi infection (5R01AI124692-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9979735. Licensed CC0.

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