Trichinella spiralis excretory-secretory antigens selectively inhibit the release of extracellular traps from neutrophils without affecting their additional antimicrobial functions

Ríos-López., Ana L.; Hernández-Bello, Romel; González, Gloria M.; Sánchez-González, Alejandro

doi:10.1016/j.cellimm.2022.104630

Cited by 6 publications

(3 citation statements)

References 49 publications

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“…Both nematodes (roundworms) and platyhelminths (flatworms) release ES molecules that potentially inhibit neutrophil-mediated NET production, thereby evading parasitic containment and elimination. Ríos-López et al (2022) proved that Trichinella spiralis (T. spiralis) ES antigens inhibited the release of NETs from neutrophils without affecting their phagocytic or chemotactic activities [70]. This observation was supported by another report that identified a novel NET inhibitory factor of the tapeworm Mesocestoides corti (M. corti).…”

Section: Helminths Evading Net-mediated Killingmentioning

confidence: 91%

NETosis in Parasitic Infections: A Puzzle That Remains Unsolved

Omar

Abdelal²

2023

IJMS

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Neutrophils are the key players in the innate immune system, being weaponized with numerous strategies to eliminate pathogens. The production of extracellular traps is one of the effector mechanisms operated by neutrophils in a process called NETosis. Neutrophil extracellular traps (NETs) are complex webs of extracellular DNA studded with histones and cytoplasmic granular proteins. Since their first description in 2004, NETs have been widely investigated in different infectious processes. Bacteria, viruses, and fungi have been shown to induce the generation of NETs. Knowledge is only beginning to emerge about the participation of DNA webs in the host’s battle against parasitic infections. Referring to helminthic infections, we ought to look beyond the scope of confining the roles of NETs solely to parasitic ensnarement or immobilization. Hence, this review provides detailed insights into the less-explored activities of NETs against invading helminths. In addition, most of the studies that have addressed the implications of NETs in protozoan infections have chiefly focused on their protective side, either through trapping or killing. Challenging this belief, we propose several limitations regarding protozoan-NETs interaction. One of many is the duality in the functional responses of NETs, in which both the positive and pathological aspects seem to be closely intertwined.

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Section: Helminths Evading Net-mediated Killingmentioning

confidence: 91%

NETosis in Parasitic Infections: A Puzzle That Remains Unsolved

Omar

Abdelal²

2023

IJMS

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“…The collected muscle larvae were washed three times with PBS buffer supplemented with 500 U/mL mycillin and transferred to RPMI 1640 medium supplemented with 500 U/mL mycillin at a density of 5000 muscle larvae/mL, then the muscle larvae were cultured in a 5% CO 2 incubator at 37 °C for 24 h [ 52 ]. Subsequently, the culture supernatant was collected and concentrated for 100-fold on a YM-3 membrane (Amicon, Beverly, MA, USA) at 4 °C, then the culture supernatant was dialyzed in saline solution for three days and the dialysate was replaced every eight hours [ 53 ]. The protein concentration of excretory-secretory antigen was determined using the Pierce™ bicinchoninic acid protein assay kit (Thermo Scientific, Waltham, MA, USA) and stored at −80 °C until use.…”

Section: Methodsmentioning

confidence: 99%

Infection of Trichinella spiralis Affects the Reproductive Capacity of ICR/CD-1 Male Mice by Reducing the Urine Pheromone Contents and Sperm Quality

Zhang

et al. 2023

IJMS

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Female mice can discriminate the urinary odors of male mice due to their olfactory acuity. Parasitic infection or subclinical infection can decrease the odor attractiveness of male mice and finally lead to aversion or avoidance responses in odor selection for female mice. Trichinella spiralis is a kind of tissue-parasitizing nematode that causes trichinellosis, a zoonotic parasitic disease that spreads throughout the world. However, the reproductive injury caused by Trichinella spiralis infection was not fully revealed. In this study, we explored the effect of Trichinella spiralis infection on the reproductive capacity in ICR/CD-1 male mice. We identified eight volatile compounds in urine by GC-MS analysis, and the results indicated that the contents of dimethyl sulfone, Z-7-tetradecen-1-ol, 6-Hydroxy-6-methyl-3-heptanone and (S)-2-sec-butyl-4,5-dihydrothiazole were significantly downregulated after parasitic infection, which might lead to the reduction of attractiveness of male mice urine to females. On the other hand, parasitic infection decreased sperm quality and downregulated the expression levels of Herc4, Ipo11, and Mrto4, and these genes were strongly related to spermatogenesis. In summary, this study revealed that the reproductive injury caused by Trichinella spiralis infection in ICR/CD-1 male mice could be associated with a decrease in urine pheromone content and sperm quality.

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“…The mechanism of this blockade is currently unknown, but it may involve inhibition, for example, of the pore-forming protein gasdermin D, which is involved in the release of DNA across the nuclear and cellular membranes ( 133 ). The authors also show that other functions of neutrophils, such as chemotaxis and phagocytosis, are not impacted by T. spiralis ES products ( 178 ).…”

Section: Immunomodulation Of Myeloid Cellsmentioning

confidence: 99%

How to train your myeloid cells: a way forward for helminth vaccines?

Doolan,

Putananickal,

Tritten

et al. 2023

Front. Immunol.

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Soil-transmitted helminths affect approximately 1.5 billion people worldwide. However, as no vaccine is currently available for humans, the current strategy for elimination as a public health problem relies on preventive chemotherapy. Despite more than 20 years of intense research effort, the development of human helminth vaccines (HHVs) has not yet come to fruition. Current vaccine development focuses on peptide antigens that trigger strong humoral immunity, with the goal of generating neutralizing antibodies against key parasite molecules. Notably, this approach aims to reduce the pathology of infection, not worm burden, with only partial protection observed in laboratory models. In addition to the typical translational hurdles that vaccines struggle to overcome, HHVs face several challenges (1): helminth infections have been associated with poor vaccine responses in endemic countries, probably due to the strong immunomodulation caused by these parasites, and (2) the target population displays pre-existing type 2 immune responses to helminth products, increasing the likelihood of adverse events such as allergy or anaphylaxis. We argue that such traditional vaccines are unlikely to be successful on their own and that, based on laboratory models, mucosal and cellular-based vaccines could be a way to move forward in the fight against helminth infection. Here, we review the evidence for the role of innate immune cells, specifically the myeloid compartment, in controlling helminth infections. We explore how the parasite may reprogram myeloid cells to avoid killing, notably using excretory/secretory (ES) proteins and extracellular vesicles (EVs). Finally, learning from the field of tuberculosis, we will discuss how anti-helminth innate memory could be harnessed in a mucosal-trained immunity-based vaccine.

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Trichinella spiralis excretory-secretory antigens selectively inhibit the release of extracellular traps from neutrophils without affecting their additional antimicrobial functions

Cited by 6 publications

References 49 publications

NETosis in Parasitic Infections: A Puzzle That Remains Unsolved

NETosis in Parasitic Infections: A Puzzle That Remains Unsolved

Infection of Trichinella spiralis Affects the Reproductive Capacity of ICR/CD-1 Male Mice by Reducing the Urine Pheromone Contents and Sperm Quality

How to train your myeloid cells: a way forward for helminth vaccines?

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