Potential application of helminth therapy for resolution of neuroinflammation in neuropsychiatric disorders

Abdoli, Amir; Ardakani, Hoda Mirzaian

doi:10.1007/s11011-019-00466-5

Cited by 8 publications

(3 citation statements)

References 165 publications

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“…Escape latency was defined as the time to find the platform during each trial and was used as an indicator of spatial learning. No statistically significant differences in the latency associated with learning the platform location (trials [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] were found between the control group (Con: 30.227±7.866 s) and infected rats (Hym: 29.357±8.845 s) during the four day trial, as evaluated by ANOVA with repeated measurements (F (1,13) = 0.036, p = 0.853).…”

Section: Acquisition Phase (Days 1-4 Trials 1-16)mentioning

confidence: 99%

Infection with intestinal helminth (Hymenolepis diminuta) impacts exploratory behavior and cognitive processes in rats by changing the central level of neurotransmitters

et al. 2022

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Parasites may significantly affect the functioning of the host organism including immune response and gut-brain-axis ultimately leading to alteration of the host behavior. The impact of intestinal worms on the host central nervous system (CNS) remains unexplored. The aim of this study was to evaluate the effect of intestinal infection by the tapeworm Hymenolepis diminuta on behavior and functions of the CNS in rats. The 3 months old animals were infected, and the effects on anxiety, exploration, sensorimotor skills and learning processes were assessed at 18 months in Open Field (OF), Novel Object Recognition (NOR) and the Water Maze (WM) tests. After completing the behavioral studies, both infected and non-infected rats were sacrificed, and the collected tissues were subjected to biochemical analysis. The levels of neurotransmitters, their metabolites and amino acids in selected structures of the CNS were determined by HPLC. In addition, the gene expression profile of the pro- and anti-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-10) was evaluated by Real-Time PCR to determine the immune response within the CNS to the tapeworm infection. The parasites caused significant changes in exploratory behavior, most notably, a reduction of velocity and total distance moved in the OF test; the infected rats exhibited decreased frequency in the central zone, which may indicate a higher level of anxiety. Additionally, parasite infestation improved spatial memory, assessed in the WM test, and recognition of new objects. These changes are related to the identified reduction in noradrenaline level in the CNS structures and less pronounced changes in striatal serotonergic neurotransmission. H. diminuta infestation was also found to cause a significant reduction of hippocampal expression of IL-6. Our results provide new data for further research on brain function during parasitic infections especially in relation to helminths and diseases in which noradrenergic system may play an important role.

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Section: Acquisition Phase (Days 1-4 Trials 1-16)mentioning

confidence: 99%

Infection with intestinal helminth (Hymenolepis diminuta) impacts exploratory behavior and cognitive processes in rats by changing the central level of neurotransmitters

et al. 2022

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“…Helminths or helminth-derived antigens display therapeutic potential for the resolution of inflammation and cytokine storm syndrome in patients with COVID-19 ( Abdoli, 2019 , Abdoli and Mirzaian Ardakani, 2020 ). Excretory-secretory molecules from Trichuris trichiura reduces intestinal inflammation by activating Th2 and Treg immune responses ( Cepon-Robins and Gildner, 2020 ; Cepon‐Robins et al, 2019).…”

Section: Immunomodulatory Role Of Helminths Against Sars-cov-2/ Covid-19: the Pros And Consmentioning

confidence: 99%

SARS-CoV-2 and helminth co-infections, and environmental pollution exposure: An epidemiological and immunological perspective

Naidoo

Ghazi

Chuturgoon

et al. 2021

Environment International

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Soil-transmitted helminths infect billions of people globally, particularly those residing in low- and middle-income regions with poor environmental sanitation and high levels of air and water pollution. Helminths display potent immunomodulatory activity by activating T helper type 2 (Th2) anti-inflammatory and Th3 regulatory immune responses. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus that causes Coronavirus disease 2019 (COVID-19), can exacerbate Th1/Th17 pro-inflammatory cytokine production in humans, leading to a cytokine storm. Air pollutants (particulate matter, oxygen radicals, hydrocarbons and volatile organic compounds) and water pollutants (metals and organic chemicals) can also intensify Th1/Th17 immune response and could exacerbate SARS-CoV-2 related respiratory distress and failure. The present review focused on the epidemiology of SARS-CoV-2, helminths and fine particulate matter 2.5 microns or less in diameter (PM 2.5 ) air pollution exposure in helminth endemic regions, the possible immunomodulatory activity of helminths against SARS-CoV-2 hyper-inflammatory immune response, and whether air and water pollutants can further exacerbate SARS-CoV-2 related cytokine storm and in the process hinder helminths immunomodulatory functionality. Helminth Th2/Th3 immune response is associated with reductions in lung inflammation and damage, and decreased expression levels of angiotensin-converting enzyme 2 (ACE2) receptors (SARS-CoV-2 uses the ACE2 receptors to infect cells and associated with extensive lung damage). However, air pollutants are associated with overexpression of ACE2 receptors in the epithelial cell surface of the respiratory tract and exhaustion of Th2 immune response. Helminth-induced immunosuppression activity reduces vaccination efficacy, and diminishes vital Th1 cytokine production immune responses that are crucial for combating early stage infections. This could be reversed by continuous air pollution exposure which is known to intensify Th1 pro-inflammatory cytokine production to a point where the immunosuppressive activities of helminths could be hindered. Again, suppressed activities of helminths can also be disadvantageous against SARS-CoV-2 inflammatory response. This “yin and yang” approach seems complex and requires more understanding. Further studies are warranted in a cohort of SARS-CoV-2 infected individuals residing in helminths and air pollution endemic regions to offer more insights, and to impact mass periodic deworming programmes and environmental health policies.

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“…The capability of Leishmania spp. to dampen NLRP3 inflammasome formation suggests that these microorganisms might be investigated for their therapeutic potential, in the area of inflammation-based diseases, similarly to parasitic nematodes, that have been proposed as agents to cure immune-mediated disorders (24,25). However, the use of pathogenic Leishmania species as potential therapeutic agents (or as source of therapeutic molecules) poses safety issues at different levels, from the preclinical to the clinical research phases and applications.…”

Section: Introductionmentioning

confidence: 99%

The non-pathogenic protozoon Leishmania tarentolae interferes with the activation of NLRP3 inflammasome in human cells: new perspectives in the control of inflammation

La Rosa,

Varotto-Boccazzi,

Saresella

et al. 2024

Front. Immunol.

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BackgroundInnate immune responses against infectious agents can act as triggers of inflammatory diseases. On the other hand, various pathogens have developed mechanisms for the evasion of the immune response, based on an inhibition of innate immunity and inflammatory responses. Inflammatory diseases could thus be controlled through the administration of pathogens or pathogen-derived molecules, capable of interfering with the mechanisms at the basis of inflammation. In this framework, the NLRP3 inflammasome is an important component in innate antimicrobial responses and a major player in the inflammatory disease. Parasites of the genus Leishmania are master manipulators of innate immune mechanisms, and different species have been shown to inhibit inflammasome formation. However, the exploitation of pathogenic Leishmania species as blockers of NLRP3-based inflammatory diseases poses safety concerns.MethodsTo circumvent safety issues associated with pathogenic parasites, we focused on Leishmania tarentolae, a species of Leishmania that is not infectious to humans. Because NLRP3 typically develops in macrophages, in response to the detection and engulfment microorganisms, we performed our experiments on a monocyte-macrophage cell line (THP-1), either wild type or knockout for ASC, a key component of NLRP3 formation, with determination of cytokines and other markers of inflammation.ResultsL. tarentolae was shown to possess the capability of dampening the formation of NLRP3 inflammasome and the consequent expression of pro-inflammatory molecules, with minor differences compared to effects of pathogenic Leishmania species.ConclusionThe non-pathogenic L. tarentolae appears a promising pro-biotic microbe with anti-inflammatory properties or a source of immune modulating cellular fractions or molecules, capable of interfering with the formation of the NLRP3 inflammasome.

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Potential application of helminth therapy for resolution of neuroinflammation in neuropsychiatric disorders

Cited by 8 publications

References 165 publications

Infection with intestinal helminth (Hymenolepis diminuta) impacts exploratory behavior and cognitive processes in rats by changing the central level of neurotransmitters

Infection with intestinal helminth (Hymenolepis diminuta) impacts exploratory behavior and cognitive processes in rats by changing the central level of neurotransmitters

SARS-CoV-2 and helminth co-infections, and environmental pollution exposure: An epidemiological and immunological perspective

The non-pathogenic protozoon Leishmania tarentolae interferes with the activation of NLRP3 inflammasome in human cells: new perspectives in the control of inflammation

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