Exploring the potential impacts of the neuronal nitric oxide synthase isoenzyme (nNOS) on the muscular stage of experimental trichinellosis in a mouse model.

Trichinella spiralis (T. spiralis) is a peculiar parasite that thrives in two biological niches within the same host: the small intestine and skeletal muscles. The persistence of the parasite during the muscular stage of infection results from a swift shift in the host's immune response toward a robust Th2 phenotype. At the same time, this tissue stage is marked by a notable expression of Th1-associated mediators, including nitric oxide (NO). Recent research has identified an unanticipated antiparasitic function of the neuronal nitric oxide synthase (nNOS) isotype during the enteral phase of trichinellosis. Yet, its impact on the muscular stage remains uncovered. For this purpose, experimental mice were infected with approximately 250 larvae of the T. spiralis strain (C+). The infected, treated groups received the anthelminthic drug albendazole T1(A), the NO donor L-arginine T2 (LA), and the nitric oxide synthase (NOS) inhibitors, aminoguanidine T3 (AG) and 7-nitroindazole T4 (7-NI). On day 35 post-infection, mice were sacrificed for parasitological, histopathological, immunohistochemical, and biochemical analyses. This research is the first to examine the distribution of nNOS in the muscle sections of T. spiralis-infected mice, which recorded weak nNOS immunostaining. Our results indicated that the neuronal (nNOS) and inducible (iNOS) isotypes failed to induce a significant elimination of the larval stages. Furthermore, unlike the intestinal stage, the study demonstrated a predominance of iNOS during muscular trichinellosis. To conclude, the two inducible and neuronal (NOS) isoforms might switch roles to meet the changing needs of NO production throughout the course of T. spiralis infection.