Background Toxocara canis infection is a neglected zoonosis associated with multisystemic involvement and persistent larval infection. Murine models are widely used to investigate host–parasite interactions, but methodological heterogeneity limits biomarker comparison and validation. Objective To characterize experimental murine T. canis infection models and synthesize parasitological, pathological, immunological, molecular, and functional biomarkers and outcomes. Methods PubMed/MEDLINE, Embase, Scopus, Web of Science Core Collection, and Virtual Health Library were searched from inception to September 1, 2026, without publication-date restrictions. Only English-language articles were eligible. Studies were screened using Rayyan and assessed according to a PECOS framework. Risk of bias and methodological quality were evaluated using SYRCLE and an adapted CAMARADES checklist. Findings were synthesized descriptively. Results Sixty-seven studies were included. The central nervous system was most investigated (39/67; 58.2%), followed by pulmonary (32/67; 47.8%) and hepatic (24/67; 35.8%) compartments. Larval recovery and tissue PCR characterized parasite localization or persistence, whereas serological, inflammatory, histopathological, molecular, and functional outcomes captured distinct dimensions of infection. Type-2-associated responses, particularly eosinophilia and IL-4, IL-5, and IL-13, were recurrent. Recent studies incorporated transcriptomics, lipidomics, extracellular-vesicle miRNAs, single-nucleus RNA sequencing, and spatial transcriptomics. Methodological limitations were particularly evident in randomization, blinding, and sample-size reporting. Conclusions Murine T. canis infection is a dynamic, multisystem process in which biomarker interpretation depends on tissue, timing, and biological context. Evidence supports complementary, purpose-driven outcome assessment rather than a single biomarker or universal protocol. Greater methodological standardization, longitudinal assessment, and multimodal designs may improve reproducibility and biomarker validation.
Primary Amoebic Meningoencephalitis (PAM), also known as Naegleriasis, has historically been rare but is re-emerging as a major public health concern. This acute, often fatal infection is caused by a free-living freshwater amoebic protozoan Naegleria fowleri, which invades the host central nervous system (CNS), inducing severe neuroinflammation. The immunopathogenesis of PAM remains poorly understood. Herein, the entire N. fowleri proteome was computationally analyzed, revealing Cathepsin B as a putative virulence factor with a potential to form a stable complex with human TLR1/2. This finding was further supported by molecular dynamics simulation analyses of the complex. Interestingly, Cathepsin B has been reported to mediate amoebic invasion of the host nasal mucosa, which reinforces our prediction. Based on these findings, a novel vaccine construct was designed using immunoreactive T and B cell epitopes from Cathepsin B and coupled with different TLR adjuvants. Computational analyses demonstrated the strong binding affinity of TLR4 adjuvant-coupled multi-epitope vaccine with TLR4, forming the most stable interactions. Theoretical immune simulation studies revealed that this vaccine elicits robust IgM and IgG responses upon triple administration, maintains B cell memory and triggers the expression of IFN-γ. Our data thus provide insight into the pathogenesis of PAM and offer a promising lead toward the development of an effective vaccine to combat the disease, which currently lacks reliable and effective treatments.
Acanthamoeba castellanii is a free-living amoeba that is found in trophozoite and cyst forms in the environment. While trophozoites rely primarily on mitochondrial oxidative phosphorylation for ATP production, cysts exhibit metabolic adaptations that enable survival under adverse conditions, including anaerobic ATP synthesis. Inorganic phosphate (Pi) plays a central role in cellular bioenergetics, as it is required for ATP synthesis. Pi uptake is mediated by specific membrane transporters that are functionally coupled to ion gradients. Emerging data indicate that inorganic phosphate transport is tightly integrated with both aerobic and anaerobic energy metabolism in A. castellanii, influencing ATP production, substrate utilization, and cellular viability. In this review, we summarize current knowledge on inorganic phosphate transport systems in A. castellanii and discuss their relationship with energy metabolism in both trophozoites and cysts.
