Eosinophils Control Liver Damage by Modulating Immune Responses Against Fasciola hepatica

Frigerio, Sofía; Costa, Valeria da; Costa, Monique; Festari, María Florencia; Landeira, Mercedes; Rodríguez-Zraquia, Santiago A.; Härtel, Steffen; Toledo, Jorge; Freire, Teresa

doi:10.3389/fimmu.2020.579801

Cited by 18 publications

(17 citation statements)

References 71 publications

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“…In contrast, there is a decrease in the prevalence of helminthic infections and other neglected diseases [16]. Therefore, it can be concluded that infection with Fasciola hepatica, as a zoonotic helminthic infection, from which [17].…”

Section: Discussionmentioning

confidence: 99%

Seroprevalence of Fasciola infection among Iranian patients hospitalized during the initial wave of COVID-19

Balazadeh¹,

Zibaei²,

Heidari³

et al. 2022

Med Srod.

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Introduction. Human fascioliasis is a zoonotic infection caused by the adult stage of the Fasciola species. Fasciola hepatica is a parasite that, following living in its vertebrate host, may reduce the host›s inflammatory immune responses to infectious diseases, including COVID-19. Therefore, because of the completely unproven and limited data on this issue, the study evaluates the prevalence of antibodies against this parasite in patients admitted to hospital due to relatively severe symptoms of COVID-19. Materials and method. During the first wave of coronavirus-19, investigations were carried out on the serum samples of 182 patients hospitalized with COVID-19, diagnosed by PCR test, and on 210 healthy subjects in Alborz province, Iran,between March -June 2020. The status of anti-Fasciola antibodies was determined in all serum samples by using the ELISA technique. A self-developed questionnaire was used to measure demographic information. Results. The frequency of Fasciola infection was found to be lesser in the COVID-19 patients than in the healthy control (n = 4, 2.2%, n = 9, 4.3%, respectively; p = 0.041). There was no significant difference between COVID-19 patients and the control group in the variables of age, education (p > 0.05). Conclusions.The study indicates that a significant association exists between Fasciola hepatica seroprevalence and the studied COVID-19 patients and healthy individuals. The results also suggest that fascioliasis may be able to lead to decreased immune responses, thereby reducing the severity and symptoms of COVID-19 disease.

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Section: Discussionmentioning

confidence: 99%

Seroprevalence of Fasciola infection among Iranian patients hospitalized during the initial wave of COVID-19

Balazadeh¹,

Zibaei²,

Heidari³

et al. 2022

Med Srod.

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“…Each experimental group contained at least four mice. PECs and hepatic leukocytes were obtained as already described [ 31 ]. Red cells were lysed with ammonium chloride potassium buffer.…”

Section: Methodsmentioning

confidence: 99%

“…Cell suspensions from PECs, livers, and spleens were washed twice with PBS containing 2% FBS and 0.1% sodium azide (FACS buffer), stained with specific antibodies for 30 min at 4 °C as previously published [ 31 ]. The following antibodies were used: anti-Sirp⍺ (P-84), -CD11c (N418), -CD86 (GL1), CD8 (53-6.7), -Siglec-F (E50-2440), -F4/80 (BM8), -CD11b (M1/70), -CD40 (HM40-3), -CD80 (16-10A1), and I-A/I-E (M5/114.15.2).…”

Section: Methodsmentioning

confidence: 99%

Heme-Oxygenase-1 Attenuates Oxidative Functions of Antigen Presenting Cells and Promotes Regulatory T Cell Differentiation during Fasciola hepatica Infection

Costa

Frigerio

et al. 2021

Antioxidants

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Fasciola hepatica is a fluke that infects livestock and humans causing fasciolosis, a zoonotic disease of increasing importance due to its worldwide distribution and high economic losses. The parasite regulates the host immune system by inducing a strong Th2 and regulatory T (Treg) cell immune response through mechanisms that might involve the expression or activity of heme-oxygenase-1 (HO-1), the rate-limiting enzyme in the catabolism of free heme that also has immunoregulatory and antioxidant properties. In this paper, we show that F. hepatica-infected mice upregulate HO-1 on peritoneal antigen-presenting cells (APC), which produce decreased levels of both reactive oxygen and nitrogen species (ROS/RNS). The presence of these cells was associated with increased levels of regulatory T cells (Tregs). Blocking the IL-10 receptor (IL-10R) during parasite infection demonstrated that the presence of splenic Tregs and peritoneal APC expressing HO-1 were both dependent on IL-10 activity. Furthermore, IL-10R neutralization as well as pharmacological treatment with the HO-1 inhibitor SnPP protected mice from parasite infection and allowed peritoneal APC to produce significantly higher ROS/RNS levels than those detected in cells from infected control mice. Finally, parasite infection carried out in gp91phox knockout mice with inactive NADPH oxidase was associated with decreased levels of peritoneal HO-1+ cells and splenic Tregs, and partially protected mice from the hepatic damage induced by the parasite, revealing the complexity of the molecular mechanisms involving ROS production that participate in the complex pathology induced by this helminth. Altogether, these results contribute to the elucidation of the immunoregulatory and antioxidant role of HO-1 induced by F. hepatica in the host, providing alternative checkpoints that might control fasciolosis.

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“…The liver migrating parasites also secrete several proteins that play a role in the reduction of pro-inflammatory responses, including the FhHDM [ 213 , 214 ] and several FABP; Fh2, Fh3, Fh15 [ 215–218 ]. In addition, interaction with the glycans associated with the parasite tegument and ES proteins has been shown to regulate the maturation and function of CD11c+ dendritic cells that are recruited to the liver, where they drive Th2/T regulatory polarization of the host immune response [ 219 ].…”

Section: Mechanisms Of Pathogenicity Of Fasciola Spp Parasitesmentioning

confidence: 99%

Pathogenicity and virulence of the liver flukesFasciola hepaticaandFasciolaGiganticathat cause the zoonosis Fasciolosis

et al. 2021

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Fasciolosis caused by the liver flukes Fasciola hepatica and Fasciola gigantica is one of the most important neglected parasitic diseases of humans and animals. The ability of the parasites to infect and multiply in their intermediate snail hosts, and their adaptation to a wide variety of mammalian definitive hosts contribute to their high transmissibility and distribution. Within the mammalian host, the trauma caused by the immature flukes burrowing through the liver parenchyma is associated with most of the pathogenesis. Similarly, the feeding activity and the physical presence of large flukes in the bile ducts can lead to anemia, inflammation, obstruction and cholangitis. The high frequency of non-synonymous polymorphisms found in Fasciola spp. genes allows for adaptation and invasion of a broad range of hosts. This is also facilitated by parasite’s excretory-secretory (ES) molecules that mediate physiological changes that allows their establishment within the host. ES contains cathepsin peptidases that aid parasite invasion by degrading collagen and fibronectin. In the bile ducts, cathepsin-L is critical to hemoglobin digestion during feeding activities. Other molecules (peroxiredoxin, cathepsin-L and Kunitz-type inhibitor) stimulate a strong immune response polarized toward a Treg/Th2 phenotype that favors fluke’s survival. Helminth defense molecule, fatty acid binding proteins, Fasciola -specific glycans and miRNAs modulate host pro-inflammatory responses, while antioxidant scavenger enzymes work in an orchestrated way to deter host oxidant-mediated damage. Combining these strategies Fasciola spp. survive for decades within their mammalian host, where they reproduce and spread to become one of the most widespread zoonotic worm parasites in the world.

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Eosinophils Control Liver Damage by Modulating Immune Responses Against Fasciola hepatica

Cited by 18 publications

References 71 publications

Seroprevalence of Fasciola infection among Iranian patients hospitalized during the initial wave of COVID-19

Seroprevalence of Fasciola infection among Iranian patients hospitalized during the initial wave of COVID-19

Heme-Oxygenase-1 Attenuates Oxidative Functions of Antigen Presenting Cells and Promotes Regulatory T Cell Differentiation during Fasciola hepatica Infection

Pathogenicity and virulence of the liver flukesFasciola hepaticaandFasciolaGiganticathat cause the zoonosis Fasciolosis

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