ABSTRACT
Trichinella infections have been documented globally and have been detected in wild and/or domestic animals except Antarctica. There is paucity of information in the metabolic responses of hosts during Trichinella infections and biomarkers for infection that can be used in the diagnosis of the disease. The current study aimed to apply a non-targeted metabolomic approach to identify Trichinella zimbabwensis biomarkers including metabolic response from sera of infected Sprague-Dawley rats. Fifty-four male Sprague-Dawley rats were randomly assigned into T. zimbabwensis infected group (n = 36) and the non-infected control (n = 18). Results from the study showed that the metabolic signature of T. zimbabwensis infection consists of enriched methyl histidine metabolism, disturbance of the liver urea cycle, impeded TCA cycle, and upregulation of gluconeogenesis metabolism. The observed disturbance in the metabolic pathways was attributed to the effects caused by the parasite during its migration to the muscles resulting in downregulation of amino acids intermediates in the Trichinella-infected animals, and therefore affecting energy production and degradation of biomolecules. It was concluded that T. zimbabwensis infection caused an upregulation of amino acids; pipecolic acid, histidine, and urea, and upregulation of glucose and meso-Erythritol. Moreover, T. zimbabwensis infection caused upregulation of the fatty acids, retinoic acid, and acetic acid. These findings highlight the potential of metabolomics as a novel approach for fundamental investigations of host-pathogen interactions as well as for disease progression and prognosis.
ABSTRACT
Malaria remains a major cause of mortality and morbidity in sub-Saharan Africa (SSA) and tissue-dwelling helminth parasites (TDHPs) are also prevalent in this region presenting a geographical overlap in endemicity. There is paucity of information on the specific host immune responses elicited at different phases of the life cycle by the co-infecting helminth parasites. This study aimed at using a laboratory animal model to determine selected chemokine, cytokine and hematological profiles in Sprague-Dawley rats co-infected with Plasmodium berghei ANKA (Pb) and a tissue-dwelling nematode, Trichinella zimbabwensis (Tz). One-hundred-and-sixty-eight male Sprague-Dawley rats (90-150g) were randomly divided into four experimental groups; Control (n = 42), Pb-infected (n = 42), Tz-infected (n = 42) and Pb + Tz-infected group (n = 42). Trichinella zimbabwensis infection (3 muscle larvae/g body weight per os) was done on day 0 while intra-peritoneal Pb infection (105 parasitised RBCs) was done at day 28 of the 42-day experimental study for the co-infection group which corresponded with day 0 of the Pb group on the protocol. Haematological parameters, cytokines (TNF-α, IL-10, IL-4, IL-6), chemokines (CXCL10, CCL5, CCL11) and burden of Tz adult worms and muscle larvae burden were determined as per need for each group. Results showed that Tz infection predisposed the co-infected animals towards rapid development of Pb parasitaemia during co-infection, reaching a higher peak percentage parasitaemia at day 7 post-infection than the Pb mono-infected group at day 6 post-infection. Animals in the co-infected group also exhibited severe anaemia, basophilia, neutrophilia, eosinophilia and lymphopenia at day 7 post Pb infection compared to the control groups. Significant elevation of Pb parasitaemia coincided with elevated pro-inflammatory cytokine TNF-α (P < 0.001), regulatory anti-inflammatory IL-10 (P < 0.001), and pro-inflammatory chemokines CXCL10 (P < 0.001) concentration in comparison to control group, at day 7 post Pb infection. Our results confirm that co-infection of Pb with Tz resulted in increased Pb parasitaemia compared to the control group in the early stages of infection and this might translate to severe malaria.
