Trichinella spiralis co-infection exacerbates Plasmodium berghei malaria-induced hepatopathy

Background: AlthoughPlasmodiumparasites and intestinal helminths share common endemic areas, the mechanisms of these co-infections on the host immune response remain not fully understood. Liver involvement in severePlasmodium falciparuminfections is a significant cause of morbidity and mortality. However, the effect of pre-existingTrichinella spiralisinfection on the immune response and liver immune-pathogenesis inP. bergheiANKA (PbANKA)-infected mice needs to be elucidated. Methods: Outbred Kunming mice were infected withT. spiralisand 9 days later were challenged withP. bergheiANKA (PbANKA), and the investigation occurred at 13 days after co-infection. Results: Compared withPbANKA-mono-infected mice,T. spiralis+PbANKA-co-infected mice had similar survival rate but lowerPbANKA parasitaemia; however, there were more severe hepatosplenomegaly, increased liver and spleen indexes, and increased liver pathology observed by hematoxylin and eosin staining; higher expression levels of galectin (Gal)-1, Gal-3, CD68(+)macrophages, and elastase-positive neutrophils measured by immunohistochemical staining; upregulated mRNA expression levels of Gal-1, Gal-3, cytokines (interferon-gamma (IFN gamma) and interleukin (IL)-6), and M1 macrophage polarization marker (inducible nitric oxide synthase (iNOS)) in the liver, and increased expression levels of Gal-1, IFN gamma, IL-6, eosinophil cationic protein, eosinophil protein X, and M1 (IL-1 beta and iNOS) and M2 (Ym1) macrophage polarization markers in the spleen of co-infected mice detected by using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR).In vitrostudy showed that compared withPbANKA-mono-infected mice, there were significantly increased expression levels of Gal-1, Gal-3, IL-6, IL-1 beta, and iNOS in the peritoneal macrophage isolated from co-infected mice detected by using qRT-PCR. Correlation analysis revealed significant positive correlations between Gal-3 and IL-1 beta in the peritoneal macrophages isolated fromPbANKA-mono-infected mice, between Gal-3 and IFN gamma in the spleen of co-infected mice, and between Gal-1 and Ym1 in the peritoneal macrophages isolated from co-infected mice. Conclusions: Our data indicate that pre-existing infection ofT. spiralismay suppressP. bergheiparasitaemia and aggravate malaria-induced liver pathology through stimulating Gal-1 and Gal-3 expression, activating macrophages, neutrophils, and eosinophils, and promoting mediator release and cytokine production.