Mucins Shed from the Laminated Layer in Cystic Echinococcosis Are Captured by Kupffer Cells via the Lectin Receptor Clec4F

Barrios, Anabella A.; Mouhape, Camila; Schreiber, Leonard; Zhang, Li; Nell, Juliane; Suárez-Martins, Mariana; Schlapp, Geraldine; Meikle, María Noel; Mulet, Ana Paula; Hsu, Tsui-Ling; Hsieh, Shie-Liang; Mourglia‐Ettlin, Gustavo; González, Carlos Alberto Bustamante; Crispo, Martina; Barth, Thomas F.E.; Casaravilla, Cecilia; Jenkins, Stephen J.; Díaz, Álvaro

doi:10.1128/iai.00031-23

Cited by 3 publications

(2 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CLRs can recognize carbohydrate structures present on the surface of many pathogens in a Ca +2 -dependent manner ( Brown et al., 2018 ). Previous studies have reported that CLRs are involved in helminth antigen recognition and influence host immune responses ( van Die and Cummings, 2010 ; Hsu et al., 2013 ; Vázquez-Mendoza et al., 2013 ; Amri and Touil-Boukoffa, 2015 ; Barrios et al., 2023 ). CLEC9A and CD205 are expressed in CD8 + BMDCs.…”

Section: Discussionmentioning

confidence: 99%

Hydatid fluid from Echinococcus granulosus induces autophagy in dendritic cells and promotes polyfunctional T-cell responses

Chop,

Ledo,

Nicolao

et al. 2024

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Parasites possess remarkable abilities to evade and manipulate the immune response of their hosts. Echinococcus granulosus is a parasitic tapeworm that causes cystic echinococcosis in animals and humans. The hydatid fluid released by the parasite is known to contain various immunomodulatory components that manipulate host´s defense mechanism. In this study, we focused on understanding the effect of hydatid fluid on dendritic cells and its impact on autophagy induction and subsequent T cell responses. Initially, we observed a marked downregulation of two C-type lectin receptors in the cell membrane, CLEC9A and CD205 and an increase in lysosomal activity, suggesting an active cellular response to hydatid fluid. Subsequently, we visualized ultrastructural changes in stimulated dendritic cells, revealing the presence of macroautophagy, characterized by the formation of autophagosomes, phagophores, and phagolysosomes in the cell cytoplasm. To further elucidate the underlying molecular mechanisms involved in hydatid fluid-induced autophagy, we analyzed the expression of autophagy-related genes in stimulated dendritic cells. Our results demonstrated a significant upregulation of beclin-1, atg16l1 and atg12, indicating the induction of autophagy machinery in response to hydatid fluid exposure. Additionally, using confocal microscopy, we observed an accumulation of LC3 in dendritic cell autophagosomes, confirming the activation of this catabolic pathway associated with antigen presentation. Finally, to evaluate the functional consequences of hydatid fluid-induced autophagy in DCs, we evaluated cytokine transcription in the splenocytes. Remarkably, a robust polyfunctional T cell response, with inhibition of Th2 profile, is characterized by an increase in the expression of il-6, il-10, il-12, tnf-α, ifn-γ and tgf-β genes. These findings suggest that hydatid fluid-induced autophagy in dendritic cells plays a crucial role in shaping the subsequent T cell responses, which is important for a better understanding of host-parasite interactions in cystic echinococcosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Hydatid fluid from Echinococcus granulosus induces autophagy in dendritic cells and promotes polyfunctional T-cell responses

Chop,

Ledo,

Nicolao

et al. 2024

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…Moreover, hepatic macrophages from S. mansoni-infected mice produce IL-6, IL-10, IL-4 and IL-13 in response to stimulation with soluble worm antigens and are thought to present worm antigens to hepatic T cells, promoting their type 2 differentiation (91). KCs are also implicated in tapeworm infection, particularly in cystic echinococcosis, as they uptake, via CLEC4F, the mucins of the laminated layer that protect the larval stages (hydatids) of Echinococcus granulosus parasites (92).…”

Section: Parasitic and Fungal Infectionsmentioning

confidence: 99%

Ontogeny, functions and reprogramming of Kupffer cells upon infectious disease

Musrati,

De Baetselier,

Movahedi

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

The liver is a vital metabolic organ that also performs important immune-regulatory functions. In the context of infections, the liver represents a target site for various pathogens, while also having an outstanding capacity to filter the blood from pathogens and to contain infections. Pathogen scavenging by the liver is primarily performed by its large and heterogeneous macrophage population. The major liver-resident macrophage population is located within the hepatic microcirculation and is known as Kupffer cells (KCs). Although other minor macrophages reside in the liver as well, KCs remain the best characterized and are the best well-known hepatic macrophage population to be functionally involved in the clearance of infections. The response of KCs to pathogenic insults often governs the overall severity and outcome of infections on the host. Moreover, infections also impart long-lasting, and rarely studied changes to the KC pool. In this review, we discuss current knowledge on the biology and the various roles of liver macrophages during infections. In addition, we reflect on the potential of infection history to imprint long-lasting effects on macrophages, in particular liver macrophages.

show abstract

The Acute Inflammatory Potential of Particles From the Echinococcus granulosus Laminated Layer Is Moderated by Its Calcium Inositol Hexakisphosphate Component

Grezzi,

González,

Díaz

et al. 2024

Parasite Immunology

Self Cite

View full text Add to dashboard Cite

Cystic echinococcosis is caused by the tissue‐dwelling larva (hydatid) of Echinococcus granulosus sensu lato. A salient feature is that this larva is protected by the acellular laminated layer (LL). As the parasite grows, the LL sheds abundant particles that can accumulate in the parasite's vicinity. The potential of LL particles to induce inflammation in vivo has not been specifically analysed. It is not known how each of its two major components, namely highly glycosylated mucins and calcium inositol hexakisphosphate (InsP6) deposits, impacts inflammation induced by the LL as a whole. In this work, we show that LL particles injected intraperitoneally cause infiltration of eosinophils, neutrophils and monocytes/macrophages as well as the disappearance of resident (large peritoneal) macrophages. Strikingly, the absence of calcium InsP6 enhanced the recruitment of all the inflammatory cell types analysed. In contrast, oxidation of the mucin carbohydrates caused decreased recruitment of neutrophils. The carbohydrate‐oxidised particles caused cell influx nonetheless, which may be explained by possible receptor‐independent effects of LL particles on innate immune cells, as suggested by previous works from our group. In summary, LL particles can induce acute inflammatory cell recruitment partly dependent on its mucin glycans, and this recruitment is attenuated by the calcium InsP6 component.

show abstract

Mucins Shed from the Laminated Layer in Cystic Echinococcosis Are Captured by Kupffer Cells via the Lectin Receptor Clec4F

Cited by 3 publications

References 57 publications

Hydatid fluid from Echinococcus granulosus induces autophagy in dendritic cells and promotes polyfunctional T-cell responses

Hydatid fluid from Echinococcus granulosus induces autophagy in dendritic cells and promotes polyfunctional T-cell responses

Ontogeny, functions and reprogramming of Kupffer cells upon infectious disease

The Acute Inflammatory Potential of Particles From the Echinococcus granulosus Laminated Layer Is Moderated by Its Calcium Inositol Hexakisphosphate Component

Contact Info

Product

Resources

About