# Therapeutic potential of hookworm proteins in promoting regulatory immune responses to modulate Trypanosoma cruzi induced liver inflammation and oxidative stress

## TL;DR

This study explores how proteins from hookworms may help reduce liver inflammation caused by a parasitic infection, without worsening the infection itself.

## Contribution

The study demonstrates the novel use of hookworm-derived proteins to modulate immune responses in T. cruzi-induced liver inflammation.

## Key findings

- AIP-1 and AIP-2 increased IFN-γ and IL-10 while reducing Nfκ-B and Stat-1 in liver tissues.
- AIP-1 uniquely upregulated Mmp9 and Btg2 gene expression.
- Treatment increased specific immune cell populations but did not affect parasite load or fibrosis.

## Abstract

Chronic Trypanosoma cruzi infection causes significant liver pathology, and current antiparasitic treatments often worsen hepatic damage. Hookworm-derived proteins have shown immunomodulatory effects in inflammatory diseases, including T. cruzi-induced myocarditis.

This study evaluates recombinant hookworm proteins AIP-1 and AIP-2 for treating liver inflammation in a murine model of chronic Chagas disease (CD).

Female BALB/c mice infected with T. cruzi were treated with AIP-1 or AIP-2 (1 mg/kg) for seven days. Controls were untreated or received aspirin (25 mg/kg) for 14 days. Liver tissues were analyzed for parasite burden (quantitative polymerase chain reaction - qPCR), histopathology (H&E, Picrosirius Red), and cytokines (multiplex assay). Splenocytes were assessed by flow cytometry, and serum was tested for liver enzyme levels.

AIP-1 and AIP-2 increased hepatic interferon gamma (IFN-γ) and interleukin 10 (IL-10), decreased Nfκ-B and Stat-1, and elevated Arg1 and Nos2 expression. AIP-1 uniquely upregulated Mmp9 and Btg2. Increased splenic CD11b⁺CD11c⁺ and CD11b⁺Ly6GloLy6C⁺ cells were observed. Despite increased immune cell infiltration, parasite load and fibrosis remained unchanged, and liver enzyme levels were stable.

AIP-1 and AIP-2 reduce hepatic inflammation and promote a balanced TH1/TH2 response, likely mediated by regulatory dendritic and myeloid-derived suppressor cells, supporting their potential as immunotherapeutic for T. cruzi-induced liver pathology.