Language
English
Publication Date
1-1-2026
Journal
Memórias do Instituto Oswaldo Cruz
DOI
10.1590/0074-02760250123
PMID
41711766
PMCID
PMC12904142
PubMedCentral® Posted Date
2-13-2026
PubMedCentral® Full Text Version
Post-print
Abstract
Background: 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.
Objective: This study evaluates recombinant hookworm proteins AIP-1 and AIP-2 for treating liver inflammation in a murine model of chronic Chagas disease (CD).
Methods: 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.
Findings: 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.
Main conclusion: 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.
Keywords
Animals, Female, Mice, Inbred BALB C, Chagas Disease, Oxidative Stress, Disease Models, Animal, Mice, Helminth Proteins, Trypanosoma cruzi, Cytokines, Flow Cytometry, Recombinant Proteins, Liver
Published Open-Access
yes
Recommended Citation
Villar, Maria Jose; Poveda, Cristina; Zhan, Bin; et al., "Therapeutic Potential of Hookworm Proteins in Promoting Regulatory Immune Responses To Modulate Trypanosoma cruzi Induced Liver Inflammation and Oxidative Stress" (2026). Faculty, Staff and Students Publications. 7035.
https://digitalcommons.library.tmc.edu/baylor_docs/7035