Integrated Cytokine and Metabolic Analysis of Pathological Responses to Parasite Exposure in Rodents (original) (raw)
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Impact of Parasitic Infections on Host Metabolism: An Overview
Indian Journal of Animal Research, Volume 58 Issue 6: 893-901 (June), 2024
The eukaryotic unicellular or multicellular hetero-specific organisms (Parasites) those are physiologically or metabolically dependent on the host for nutrition and shelter can cause diverse impact in the host patho-physiology by manipulating their immune system. The impact of parasitic infections on host metabolism can have far-reaching consequences depending on the type of parasite, the location of the infection and the duration of the infection which may include growth stunting, cognitive impairment and increased susceptibility to other diseases. Understanding these metabolic effects is crucial for developing effective strategies to prevent and treat parasitic infections, as well as mitigating their long-term consequences on host health and development. The parasites have deleterious morbid effect on the body of the host that leads to the secondary metabolic disorders like diabetes, hypertension and cardiovascular disorders. Beside these, parasites aids in the alteration of the cellular regulation of the affected host and microbiota of the gut cells. In this review the positive and negative feedback of the parasites on the host with exemplary illustrations has been discussed.
International Journal for Parasitology, 2009
In order to enhance our understanding of physiological and pathological consequences of a patent Schistosoma mansoni infection in the mouse, we examined the metabolic responses of different tissue samples recovered from the host animal using a metabolic profiling strategy. Ten female NMRI mice were infected with $80 S. mansoni cercariae each, and 10 uninfected age-and sex-matched animals served as controls. At day 74 post infection (p.i.), mice were killed and jejunum, ileum, colon, liver, spleen and kidney samples were removed. We employed 1 H magic angle spinning-nuclear magnetic resonance spectroscopy to generate tissue-specific metabolic profiles. The spectral data were analyzed using multivariate modelling methods including an orthogonal signal corrected-projection to latent structure analysis and hierarchical principal component analysis to assess the differences and/or similarities in metabolic responses between infected and non-infected control mice. Most tissues obtained from S. mansoni-infected mice were characterized by high levels of amino acids, such as leucine, isoleucine, lysine, glutamine and asparagine. High levels of membrane phospholipid metabolites, including glycerophosphoryl choline and phosphoryl choline were found in the ileum, colon, liver and spleen of infected mice. Additionally, low levels of energy-related metabolites, including lipids, glucose and glycogen were observed in ileum, spleen and liver samples of infected mice. Energy-related metabolites in the jejunum, liver and renal medulla were found to be positively correlated with S. mansoni worm burden upon dissection. These findings show that a patent S. mansoni infection causes clear disruption of metabolism in a range of tissues at a molecular level, which can be interpreted in relation to the previously reported signature in a biofluid (i.e. urine), giving further evidence of the global effect of the infection.
Chemometric analysis of biofluids from mice experimentally infected with Schistosoma mansoni
Parasites & Vectors, 2011
Background: The urinary metabolic fingerprint of a patent Schistosoma mansoni infection in the mouse has been characterized using spectroscopic methods. However, the temporal dynamics of metabolic alterations have not been studied at the systems level. Here, we investigated the systems metabolic changes in the mouse upon S. mansoni infection by modeling the sequence of metabolic events in urine, plasma and faecal water.
Metabolic alterations in the hamster co-infected with Schistosoma japonicum and Necator americanus
International Journal for Parasitology, 2010
Co-infection with hookworm and schistosomes is a common phenomenon in sub-Saharan Africa, as well as in parts of South America and southeast Asia. As a first step towards understanding the metabolic response of a hookworm-schistosome co-infection in humans, we investigated the metabolic consequences of co-infection in an animal model, using a nuclear magnetic resonance (NMR)-based metabolic profiling technique, combined with multivariate statistical analysis. Urine and serum samples were obtained from hamsters experimentally infected with 250 Necator americanus infective L 3 and 100 Schistosoma japonicum cercariae simultaneously. In the co-infection model, similar worm burdens were observed as reported for single infection models, whereas metabolic profiles of co-infection represented a combination of the altered metabolite profiles induced by single infections with these two parasites. Consistent differences in metabolic profiles between the co-infected and non-infected control hamsters were observed from 4 weeks p.i. onwards. The predominant metabolic alterations in co-infected hamsters consisted of depletion of amino acids, tricarboxylic acid cycle intermediates (e.g. citrate and succinate) and glucose. Moreover, alterations of a series of gut microbial-related metabolites, such as decreased levels of hippurate, 3-hydroxyphenylpropionic acid, 4-hydroxyphenylpropionic acid and trimethylamine-N-oxide, and increased concentrations of 4-cresol glucuronide and phenylacetylglycine were associated with co-infection. Our results provide a first step towards understanding the metabolic response of an animal host to multiple parasitic infections.
Using metabolomics to dissect host–parasite interactions
Current Opinion in Microbiology, 2016
Protozoan parasites have evolved diverse growth and metabolic strategies for surviving and proliferating within different extracellular and intracellular niches in their mammalian hosts. Metabolomic approaches, including high coverage metabolite profiling and 13 C/ 2 H-stable isotope labeling, are increasingly being used to identify parasite metabolic pathways that are important for survival and replication in vivo. These approaches are highlighting new links between parasite carbon metabolism and the ability of different parasite stages to colonize specific niches or host cell types. They have also revealed novel metabolic regulatory mechanisms that are important for homeostasis and survival in potentially nutrient variable environments. These studies highlight the importance of parasite and host metabolism as determinants of host-parasite interactions.
The observation that experimental helminth infection can be associated with immunomodulation and suppression of inflammatory diseases at distal tissue sites, has been used as rationale for trialing helminths such asNecator americanusfor the treatment of inflammatory disorders in humans. However, the lack of sufficient knowledge of the immunological interplay between human host and parasite in a controlled infection setting limits ongoing clinical intervention studies. In this one-year longitudinal study, healthy volunteers were recruited and infected withN. americanus. Changes in immune responses, microbiome, plasma metabolome and gut physiology were examined over the course of the one-year period. All participants were successfully infected as confirmed by detectable eggs in the feces and adult worms visualized in the intestine. In general, individual variation in immune cells, serum cytokines, fecal microbiome and plasma metabolites were greater than changes induced by the infecti...
Frontiers in microbiology, 2018
Pathogenic trypanosomatids (, and spp.) are protozoan parasites that cause neglected diseases affecting millions of people in Africa, Asia, and the Americas. In the process of infection, trypanosomatids evade and survive the immune system attack, which can lead to a chronic inflammatory state that induces cumulative damage, often killing the host in the long term. The immune mediators involved in this process are not entirely understood. Most of the research on the immunologic control of protozoan infections has been focused on acute inflammation. Nevertheless, when this process is not terminated adequately, permanent damage to the inflamed tissue may ensue. Recently, a second process, called resolution of inflammation, has been proposed to be a pivotal process in the control of parasite burden and establishment of chronic infection. Resolution of inflammation is an active process that promotes the normal function of injured or infected tissues. Several mediators are involved in thi...
Pathogen manipulation of host metabolism: A common strategy for immune evasion
PLOS Pathogens
The immune system is one of the three main consumers of energy in the human body; brain, muscle, and the immune system use similar amounts (approximately 500 kcal/day) [1]. Rapid bursts of cellular proliferative, biosynthetic, and secretory activities by leukocytes require considerable metabolic resources that are especially important during periods of infection and inflammation [2, 3]. Because immune cells have negligible intracellular nutrient stores and rely on aerobic glycolysis for activation and proliferation, they are particularly dependent on the uptake of metabolic substrates [2-6]. Indeed, glucose uptake is the primary limiting factor in T-cell activation [5, 6]. T-cell activation and proliferation are decreased in low-glucose states along with reduced production of cytokine effectors of the immune response, including interferon γ (IFN-γ) [6-8]. Susceptibility to infections by individuals with metabolic diseases further underscores the significant impact of metabolic disruption on the functions of innate and adaptive immunity [9, 10]. Pathogens that are well adapted to their hosts have developed an extraordinarily wide range of mechanisms to modulate host immunity in order to facilitate and prolong infection and transmission. Several of these mechanisms are relatively well characterized and appear to act directly on host target tissues. Traditionally, the effects that many pathogens have on host metabolism have been assumed to be downstream consequences of pathogenesis. However, increasing evidence suggests that these pathogen-induced metabolic disturbances may instead reflect aspects of the pathogens' modulation of the immune response to enhance and/or prolong the period of infection and transmissibility (Fig 1). Here, we examine three diverse but highly prevalent global pathogens that disrupt host metabolism during infection and may thereby alter the host immune response: Trypanosoma cruzi, Plasmodium falciparum, and Bordetella pertussis, responsible for Chagas disease, malaria, and whooping cough, respectively. Considering how metabolic changes that pathogens induce in the host can affect the immune response may reveal commonalities that can contribute to understanding, controlling, and treating a wide range of diseases.
Frontiers in microbiology, 2018
is the etiologic agent of Chagas' disease, which affects 6-7 million people worldwide. Different strains of present specific genotypic and phenotypic characteristics that affect the host-pathogen interactions, and thus, the parasite has been classified into six groups (TcI to TcVI). infection presents two clinical phases, acute and chronic, both with distinct characteristics and important participation by the immune system. However, the specific contributions of parasite and host factors in the disease phases are not yet fully understood. The murine model for Chagas' disease is well-established and reproduces important features of the human infection, providing an experimental basis for the study of host lineages and parasite strains. Thus, we evaluated acute and chronic infection by the G (TcI) and CL (TcVI) strains of , which have distinct tropisms and infectivity, in two inbred mice lineages (C57BL/6 and BALB/c) that display variable degrees of susceptibility to different...
OnLine Journal of Biological Sciences, 2015
The study of biotherapies as an intervention in experimental models of infection is a possible means to understand the effects of these highly diluted medications. The present study evaluated the immunological and parasitological effects of biotherapies that were prepared from mouse serum that was uninfected (sarcode: BSNI 13cH group) and chronically infected with the Y strain of T. cruzi (nosode: BSI 13cH group), dynamization 13cH, in male Swiss mice at 28 days of age. On days 0 and 12 after infection (a.i.), the BSNI 13cH group exhibited a pronounced Th1 response that was attributable to a reduction of interleukin-4 (IL-4) concentrations, with no significant differences in interferon-γ (IFN-γ) concentrations and a decrease in IL-17A concentrations on day 0 a.i. compared with the control and BSI 13cH groups. However, this cytokine balance was not sufficient to alter blood parasitemia in treated animals, likely because of a decrease in IFN-γ concentrations on day 8 a.i., thus hindering a more effective Th1 response. In contrast, the BSI 13cH group presented a pronounced Th2 response that was attributable to an increase in IL-4 concentrations (on days 0 and 8 a.i.) and a decrease in IFN-γ concentration (on day 12 a.i.) compared with the control and BSNI 13cH groups. This cytokine balance suppressed the immune response to T. cruzi in murine infection, resulting in a significant increase in blood parasitemia, decrease in the patent period and subsequently a decrease in survival time. The results indicate that these highly diluted medications differentially modulate the immune system and represent a substantial contribution to the field of homeopathic medicine, providing evidence of the action of these medications.