scholarly journals Intestinal epithelial cell secretion of RELM-β protects against gastrointestinal worm infection

2009 ◽  
Vol 206 (13) ◽  
pp. 2947-2957 ◽  
Author(s):  
De'Broski R. Herbert ◽  
Jun-Qi Yang ◽  
Simon P. Hogan ◽  
Kathryn Groschwitz ◽  
Marat Khodoun ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Trichinella Spiralis ◽  
Intestinal Lumen ◽  
Th2 Cells ◽  
Nippostrongylus Brasiliensis ◽  
Intestinal Epithelial ◽  
Cell Secretion ◽  
Heligmosomoides Polygyrus ◽  
Parasitic Helminths

Th2 cells drive protective immunity against most parasitic helminths, but few mechanisms have been demonstrated that facilitate pathogen clearance. We show that IL-4 and IL-13 protect against intestinal lumen-dwelling worms primarily by inducing intestinal epithelial cells (IECs) to differentiate into goblet cells that secrete resistin-like molecule (RELM) β. RELM-β is essential for normal spontaneous expulsion and IL-4–induced expulsion of Nippostrongylus brasiliensis and Heligmosomoides polygyrus, which both live in the intestinal lumen, but it does not contribute to immunity against Trichinella spiralis, which lives within IEC. RELM-β is nontoxic for H. polygyrus in vitro but directly inhibits the ability of worms to feed on host tissues during infection. This decreases H. polygyrus adenosine triphosphate content and fecundity. Importantly, RELM-β–driven immunity does not require T or B cells, alternative macrophage activation, or increased gut permeability. Thus, we demonstrate a novel mechanism for host protection at the mucosal interface that explains how stimulation of epithelial cells by IL-4 and IL-13 contributes to protection against parasitic helminthes that dwell in the intestinal lumen.

Induction of surface fluidity in Trichinella spiralis larvae during penetration of the host intestine: simulation by cyclic AMP in vitro

Parasitology ◽  
1997 ◽  
Vol 114 (1) ◽  
pp. 71-77 ◽  
Author(s):  
J. MODHA ◽  
M. C. ROBERTS ◽  
M. W. KENNEDY ◽  
J. R. KUSEL
Keyword(s):  
Cyclic Amp ◽  
Trichinella Spiralis ◽  
Lateral Diffusion ◽  
Epithelial Tissue ◽  
Intestinal Epithelial ◽  
Parasitic Helminths ◽  
Intracellular Parasites ◽  
Fluid Properties ◽  
Lipid Probe

The lateral diffusion (DL) properties of the fluorescent lipid probe 5-N (octadecanoyl) aminofluorescein (AF18) inserted into the surface of muscle-stage larvae of Trichinella spiralis were investigated by fluorescence recovery after photobleaching. AF18 was not free to diffuse laterally in dormant larvae, and this remained unchanged after larval activation in vitro with trypsin and bile. However, a significant increase in surface fluidity of the probe was demonstrated (%R = 74·5; DL = 11·5 × 10−9 cm2/sec) when larvae invaded intestinal epithelial tissue following oral infection of mice. Membrane-permeant photoactivatable caged cyclic AMP was used to analyse the putative mechanism responsible for this increase in lateral diffusion in the parasite surface. Although incubation of larvae with 1–50 μM caged cAMP had no effect on surface fluidity, incubation with 100 μM caged cAMP induced a substantial increase in the lateral mobility of AF18 (%R = 64·3; DL = 8·3 × 10−11 cm2/sec) immediately following photo-activation of the caged messenger. This induced fluidity, however, was transient and the larval surface reverted to immobility within 15 min. These observations constitute the first reported measurement of the fluid properties of the surface of intracellular parasites, the first demonstration of the parasite surface fluidity altering as a result of host cell invasion and the first indication of a mechanism underlying changes in surface fluidity in parasitic helminths.

Effect of dietary condensed tannins on gastrointestinal nematodes

2001 ◽  
Vol 137 (4) ◽  
pp. 461-469 ◽  
Author(s):  
N. L. BUTTER ◽  
J. M. DAWSON ◽  
D. WAKELIN ◽  
P. J. BUTTERY
Keyword(s):  
Condensed Tannins ◽  
Trichinella Spiralis ◽  
Condensed Tannin ◽  
Intestinal Lumen ◽  
Parasitic Nematodes ◽  
Nippostrongylus Brasiliensis ◽  
Small Intestinal Mucosa ◽  
Quebracho Tannin ◽  
Small Intestinal

It has been previously shown in this laboratory that feeding a model condensed tannin, quebracho tannin, reduces the small intestinal nematode burden in sheep and rats. The aim of the current programme was to determine whether this occurs through direct toxicity against the parasites. Both in vivo and in vitro studies were conducted. The first study compared the effect of dietary quebracho tannin (40 g/kg) on the establishment of the parasitic nematodes Nippostrongylus brasiliensis and Trichinella spiralis in the rat small intestine. The burden of N. brasiliensis, which, although closely associated with the mucosa, actually dwells within the small intestinal lumen, was significantly reduced (P<0·001) by dietary quebracho tannin. In contrast, T. spiralis, which penetrates into the small intestinal mucosa, was unaffected (>0·05) by the dietary inclusion of quebracho tannin. The second study involved monitoring the survival of adult N. brasiliensis and T. spiralis when incubated in vitro in varying concentrations of quebracho tannin in Hanks’ balanced salt solution. The survival of N. brasiliensis was compromised at concentrations as low as 0·01% (w/v) quebracho tannin but improved with the addition of 0·1% (w/v) polyethylene glycol, which binds to, and inactivates, tannin. T. spiralis was similarly affected, but much more rapidly. These results suggest that dietary quebracho tannin may reduce nematode worm burdens through a toxic effect that requires direct contact between parasite and tannin. This raises the possibility that feeding locally available plant material containing condensed tannins may be an alternative method for controlling parasite infections, especially in areas such as the tropics and subtropics.

scholarly journals RNAi-mediated silencing of Trichinella spiralis serpin-type serine protease inhibitors results in a reduction in larval infectivity

2020 ◽  
Vol 51 (1) ◽  
Author(s):  
Nana Yi ◽  
Pengcheng Yu ◽  
Lijia Wu ◽  
Zhaokun Liu ◽  
Jingzhe Guan ◽  
...  
Keyword(s):  
Survival Rate ◽  
Epithelial Cells ◽  
Serine Protease ◽  
Protease Inhibitors ◽  
Intestinal Epithelial Cells ◽  
Trichinella Spiralis ◽  
Intestinal Epithelial ◽  
Serine Protease Inhibitors

AbstractTrichinella spiralis serpin-type serine protease inhibitors (TsSPIs) are expressed in adult worms (AW), newborn larvae (NBL) and muscle larvae (ML) of T. spiralis, with the ML stage demonstrating the highest expression level. This study aims to determine TsSPI functions in larval viability and invasion of intestinal epithelial cells in vitro, as well as their development, survival, and fecundity in vivo via RNAi. TsSPI-specific siRNAs and dsRNA were transfected into ML by incubation. The silencing effect of TsSPI transcription and expression was determined using qPCR and western blot, respectively. After incubation in 60 ng/μL dsRNA–TsSPI for 3 days, larval TsSPI mRNA and protein expression levels were reduced by 68.7% and 68.4% (P < 0.05), respectively. dsRNA-mediated silencing of TsSPI significantly impacted larval invasion into intestinal epithelial cells in vitro but did not affect the survival rate of larvae. After challenge with dsRNA–TsSPI-treated ML, mice exhibited a 56.0% reduction in intestinal AW burden and 56.9% reduction in ML burden (P < 0.05), but NBL production of female AW remained the same (P > 0.05). Our results revealed that RNAi-mediated silencing of TsSPI expression in T. spiralis significantly reduced larval infectivity and survival in the host but had no effect on the survival rate and fecundity. Furthermore, TsSPIs have no effect on the growth and reproduction of parasites but may be directly involved in regulating the interaction of T. spiralis and the host. Therefore, TsSPIs are crucial in the process of T. spiralis larval invasion and parasite survival in the host.

scholarly journals Neonatal Mouse Gut Metabolites Influence Cryptosporidium parvum Infection in Intestinal Epithelial Cells

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. e02582-20
Author(s):  
Kelli L. VanDussen ◽  
Lisa J. Funkhouser-Jones ◽  
Marianna E. Akey ◽  
Deborah A. Schaefer ◽  
Kevin Ackman ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Epithelial Cells ◽  
Cryptosporidium Parvum ◽  
Intestinal Epithelial Cells ◽  
Saturated Fatty Acids ◽  
Intestinal Lumen ◽  
Intestinal Epithelial ◽  
Content Type ◽  
Long Chain

ABSTRACTThe protozoan parasite Cryptosporidium sp. is a leading cause of diarrheal disease in those with compromised or underdeveloped immune systems, particularly infants and toddlers in resource-poor localities. As an enteric pathogen, Cryptosporidium sp. invades the apical surface of intestinal epithelial cells, where it resides in close proximity to metabolites in the intestinal lumen. However, the effect of gut metabolites on susceptibility to Cryptosporidium infection remains largely unstudied. Here, we first identified which gut metabolites are prevalent in neonatal mice when they are most susceptible to Cryptosporidium parvum infection and then tested the isolated effects of these metabolites on C. parvum invasion and growth in intestinal epithelial cells. Our findings demonstrate that medium or long-chain saturated fatty acids inhibit C. parvum growth, perhaps by negatively affecting the streamlined metabolism in C. parvum, which is unable to synthesize fatty acids. Conversely, long-chain unsaturated fatty acids enhanced C. parvum invasion, possibly by modulating membrane fluidity. Hence, gut metabolites, either from diet or produced by the microbiota, influence C. parvum growth in vitro and may also contribute to the early susceptibility to cryptosporidiosis seen in young animals.IMPORTANCECryptosporidium sp. occupies a unique intracellular niche that exposes the parasite to both host cell contents and the intestinal lumen, including metabolites from the diet and produced by the microbiota. Both dietary and microbial products change over the course of early development and could contribute to the changes seen in susceptibility to cryptosporidiosis in humans and mice. Consistent with this model, we show that the immature gut metabolome influenced the growth of Cryptosporidium parvumin vitro. Interestingly, metabolites that significantly altered parasite growth were fatty acids, a class of molecules that Cryptosporidium sp. is unable to synthesize de novo. The enhancing effects of polyunsaturated fatty acids and the inhibitory effects of saturated fatty acids presented in this study may provide a framework for future studies into this enteric parasite’s interactions with exogenous fatty acids during the initial stages of infection.

scholarly journals Molting, Ecdysis, and Reproduction of Trichinella spiralis Are Supported In Vitro by Intestinal Epithelial Cells

2002 ◽  
Vol 70 (4) ◽  
pp. 1853-1859 ◽  
Author(s):  
L. F. Gagliardo ◽  
C. S. McVay ◽  
J. A. Appleton
Keyword(s):  
Life Cycle ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Trichinella Spiralis ◽  
Mature Male ◽  
In Vitro Cultivation ◽  
Low Density ◽  
Intestinal Epithelial ◽  
Prolonged Culture

ABSTRACT Trichinella spiralis is an obligate parasite of animals that has an unusual intracellular life cycle. Investigation of parasitism at the cellular and molecular levels has been challenging because of a shortage of tools for in vitro cultivation of T. spiralis. We have found that T. spiralis larvae molt, ecdyse, develop to adulthood, and reproduce when they are inoculated onto cultured intestinal epithelial cells. Initially, larvae invade and migrate through cells in a monolayer (T. ManWarren, L. Gagliardo, J. Geyer, C. McVay, S. Pearce-Kelling, and J. Appleton, Infect. Immun. 65:4806-4812, 1997). During prolonged culture in Caco-2 epithelial cells, L1 larvae molted and ecdysed with efficiencies as high as 50%. Molting and ecdysis in vitro required entry of the parasite into cells; conditions that prevented entry into cells also prevented ecdysis. When larvae were inoculated at a low density and cultured for 5 to 9 days, as many as 50% of the larvae developed to adult stages. Low numbers of mature male worms with copulatory appendages were observed in these cultures. The majority of worms that survived for five or more days were unfertilized females. Low-density cultures supported development of female worms with embryos at rates of 4 to 5%. These results show that the intestinal life cycle of T. spiralis can be supported entirely by host epithelial cells. Our model should allow more detailed investigation of intracellular parasitism by T. spiralis.

Direct effects of IL-4/IL-13 and the nematode Nippostrongylus brasiliensis on intestinal epithelial cells in vitro

2010 ◽  
Vol 32 (6) ◽  
pp. 420-429 ◽  
Author(s):  
K. TAKEDA ◽  
K. HASHIMOTO ◽  
R. UCHIKAWA ◽  
T. TEGOSHI ◽  
M. YAMADA ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Nippostrongylus Brasiliensis ◽  
Intestinal Epithelial ◽  
Direct Effects

Nematocide activity of 6,7-diarylpteridines in three experimental models

1999 ◽  
Vol 73 (4) ◽  
pp. 333-336 ◽  
Author(s):  
C. Ochoa ◽  
M. Rodríguez ◽  
L. Domínguez ◽  
J. Saldaña ◽  
R. Di Maio ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Trichinella Spiralis ◽  
Experimental Models ◽  
Moderate Activity ◽  
Nippostrongylus Brasiliensis ◽  
Heligmosomoides Polygyrus ◽  
Method Of Evaluation ◽  
Pteridine Derivatives

Thein vitronematocide activity of seventeen 6,7-diarylpteridines has been tested using three different experimental models,Caenorhabditis elegans,Nippostrongylus brasiliensisandHeligmosomoides polygyrus. The method of evaluation of inhibition in the secretion of acetylcholinesterase byH. polygyrusseems to be the most indicated to avoid false positives. Thein vivoactivities, againstTrichinella spiralis, of the mostin vitroactive pteridines have been assayed. All pteridine derivatives bearing 6,7-di-p-bromophenyl substituents have shownin vitronematocide activites in the three experimental models used. Amongst all the pteridines testedin vivo, only 2,4-pteridinedithione derivatives exhibited moderate activity.

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