scholarly journals Rapid purification and characterization of l-dopachrome-methyl ester tautomerase (macrophage-migration-inhibitory factor) from Trichinella spiralis, Trichuris muris and Brugia pahangi

1998 ◽  
Vol 335 (3) ◽  
pp. 495-498 ◽  
Author(s):  
Joanne L. PENNOCK ◽  
Jerzy M. BEHNKE ◽  
Quentin D. BICKLE ◽  
Eileen DEVANEY ◽  
Richard K. GRENCIS ◽  
...  

Macrophage-migration-inhibition factor (MIF) is an essential stimulator of mammalian T-lymphocyte-dependent adaptive immunity, hence MIF orthologues might be expressed by infectious organisms as an immunosubversive stratagem. Since MIF actively catalyses the tautomerization of the methyl ester of l-dopachrome (using dopachrome tautomerase), the occurrence of MIF orthologues in several parasitic helminths was investigated by assaying and characterizing such activity. Evidence of MIF orthologues (dopachrome tautomerase) was found in the soluble fraction of the nematodes Trichinella spiralis (stage 4 larvae) and Trichuris muris (adults), and the filarial nematode Brugia pahangi (adults). The MIF orthologues of Tr. muris(TmMIF) and B. pahangi (BpMIF) were purified to homogeneity using phenyl-agarose chromatography, that of T. spiralis (TsMIF) required a further step: cation-exchange FPLC. Retention time on reverse-phase HPLC and Mr on SDS/PAGE of the nematode MIFs were similar to those of human MIF. N-terminal sequences (19 residues) of TsMIF and TmMIF showed 47 and 36% identity, respectively, with human MIF. The N-terminal sequence of BpMIF (14 residues) was identical to that of an MIF orthologue in the genome of B. malayi (Swiss-Prot, P91850) and showed 43% identity to either human or TsMIF. TsMIF had 10-fold higher dopachrome tautomerase activity than MIF from the other sources. The enzyme activities of TsMIF, BpMIF and TmMIF were less sensitive to inhibition by haematin (I50: > 15 µM, > 15 µM and 2.6 µM, respectively) than that of human MIF (I50 0.2 µM). Significant dopachrome tautomerase or phenyl-agarose-purifiable MIF-like protein was not detected in the soluble fraction of the nematodes Heligmosomoides polygyrus and Nippostrongylus brasiliensis, the cestode Hymenolepis diminuta, or the trematodes Schistosoma mansoni, S. japonicum and S. haematobium, or the free-living nematode, Caenorhabditis elegans, which does contain an MIF-related gene.

2009 ◽  
Vol 206 (13) ◽  
pp. 2947-2957 ◽  
Author(s):  
De'Broski R. Herbert ◽  
Jun-Qi Yang ◽  
Simon P. Hogan ◽  
Kathryn Groschwitz ◽  
Marat Khodoun ◽  
...  

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.


2003 ◽  
Vol 77 (2) ◽  
pp. 125-131 ◽  
Author(s):  
Y.R. Mahida

AbstractIn rodents,Trichinella spiralisandNippostrongylus brasiliensisinfect the small intestine andTrichuris murisresides in the colon. The intestinal host response in these animals is characterized by changes in mucosal architecture and inflammation and is associated with worm expulsion. The requirement of T cell-mediated host response in worm expulsion has been demonstrated over many years. Subsequent studies have shown that Th2-type, but not Th1-type, responses mediate resistance to the nematodes. Investigations using neutralizing antibodies and genetically manipulated mice have characterized the contribution of individual Th2-type cytokines in not only worm expulsion, but also specific cellular changes that occur in the mucosa, such as alterations in epithelial phenotype and smooth muscle. There is also increasing appreciation of the contribution of non-bone marrow-derived cells in innate and adaptive host responses in these models.


2017 ◽  
Vol 54 (2) ◽  
pp. 170-173 ◽  
Author(s):  
N. Cigarroa-Toledo ◽  
Y. De Los Santos-Martinez ◽  
C. V. Zaragoza-Vera ◽  
M. M. Garcia-Rodriguez ◽  
C. M. Baak-Baak ◽  
...  

Summary The aim of this study was to determine the prevalence and species composition of helminths in commensal rodents captured inside private residences in the city of Villahermosa in Tabasco, Mexico. Trapping was performed at each house for three consecutive nights from October to December 2015. Fifty commensal rodents were captured: 23 Rattus norvegicus, 16 Mus musculus and 11 Rattus rattus. Rodents were transported alive to the laboratory and held in cages until they defecated. Feces were analyzed for helminth eggs using the Sheather’s flotation technique. The overall prevalence of helminths in rodents was 60 %: R. norvegicus was more likely to be parasitized (87.0 %) than R. rattus (63.6 %) and M. musculus (18.8 %). Eggs from at least 13 species of helminths were identified: Hymenolepis diminuta, Rodentolepis nana, Moniliformis moniliformis, Heligmosomoides polygyrus, Heterakis spumosa, Mastophorus muris, Nippostrongylus brasiliensis, Strongyloides ratti, Syphacia obvelata, Syphacia muris, Toxocara sp., Trichosomoides crassicauda, and Trichuris muris. This is the first study to report the presence of H. polygyrus, S. ratti and T. crassicauda in commensal rodents in Mexico. In conclusion, our results suggest that helminths commonly infect commensal rodents in Villahermosa and therefore rodents present a health risk to inhabitants in this region.


2010 ◽  
Vol 62 (4) ◽  
pp. 1091-1100 ◽  
Author(s):  
D. Kataranovski ◽  
Milena Kataranovski ◽  
Isidora Deljanin

The aims of this study were to provide baseline knowledge about intestinal parasites in Norway rats (Rattus norvegicus) that inhabit the Belgrade area, and to analyze the associations among helminths. Of 302 trapped rats, 52% were females and 48% males, with 39% and approx. 37% of juvenile-subadult individuals, per sex, respectively. The following parasites were detected (with their respective prevalence): Cestoda - Hymenolepis diminuta (30.46%) and Rodentolepis fraterna (12.58%); Nematoda - Heterakis spumosa (36.75%), Nippostrongylus brasiliensis (16.22%), Capillaria sp. (5.96%), Trichuris muris (5.96%), Syphacia muris (4.30%) and Strongylus sp. larvae (0.33%). Flukes (Trematoda) were not recorded. Of all examined rats, 68.54% were found to harbor at least one parasite species, with higher prevalence in male hosts and in adult individuals. There were no age-related differences in the prevalence of infection with individual helminth species. Multiple infections occurred with up to four species per rat showing different combinations of parasite infections. These are the first records of the gastrointestinal helminth fauna of Norway rats in Serbia.


2019 ◽  
Vol 94 ◽  
Author(s):  
J.A. Panti-May ◽  
E.E. Palomo-Arjona ◽  
Y.M. Gurubel-González ◽  
R.C. Barrientos-Medina ◽  
M.C. Digiani ◽  
...  

Abstract The black rat Rattus rattus and the house mouse Mus musculus are two commensal rodent species that harbour and shed zoonotic pathogens, including helminths. The aim of this survey was to study the helminth community and the patterns of infections in R. rattus and M. musculus from two Mayan communities in Mexico. Gastrointestinal helminths were isolated from 322 M. musculus and 124 R. rattus, including Gongylonema neoplasticum, Hassalstrongylus aduncus, Hassalstrongylus musculi, Hydatigera taeniaeformis metacestode, Hymenolepis diminuta, Nippostrongylus brasiliensis, Oligacanthorhynchidae gen. sp., Syphacia muris, Syphacia obvelata, Rodentolepis microstoma and Trichuris muris. The overall richness of helminths was seven in R. rattus and six in M. musculus. The results of generalized linear models showed that juvenile rodents had lower probabilities of being infected with G. neoplasticum, H. taeniaeformis and H. musculi than adult rodents. A positive association between the prevalence of S. muris and rat abundance was found. The intensity of infection with S. muris was higher in the rainy season than in the dry season; the opposite result was found for H. musculi infection. Male R. rattus harboured more S. muris specimens. The intensity of infection with T. muris was inversely associated with mouse abundance. The presence of the zoonotic H. diminuta, as well as H. taeniaeformis and R. microstoma in rodent populations indicates that there is risk of transmission, and that their entire life cycle occurs in the study area.


2017 ◽  
Vol 54 (3) ◽  
pp. 231-239 ◽  
Author(s):  
J. A. Panti-May ◽  
E. Palomo-Arjona ◽  
Y. Gurubel-González ◽  
M. A. Torres-Castro ◽  
V. M. Vidal-Martínez ◽  
...  

SummaryThe aim of this paper was to study the occurrence of helminths inMus musculusandRattus rattusfrom urban, suburban and rural settlements in Yucatán, Mexico; and to analyse the host factors (e.g. sex) related to helminths’ distribution. Helminths in a total of 279 rodents were surveyed by visual examination of the liver for metacestodes and faecal examination for helminth eggs using the formalin-ethyl acetate sedimentation technique. The cestodesHydatigera taeniaeformis(metacestodes detected in the liver) andHymenolepis diminuta,and the nematodesAspiculurissp.,Nippostrongylus brasiliensis,Syphacia muris,Syphacia obvelata, andTrichuris muriswere identified. InM. musculus, the prevalence of infection withT. murisandH. taeniaeformiswas higher in the rural village compared to those in the suburban neighbourhood. ForR. rattus, a higher prevalence of infection withH. diminutawas found in the urban site compared to that in the suburban site. This study reports the occurrence ofH. diminutaamong rodents living in close proximity to humans, representing a potential public health risk. In addition, this survey increases our understanding of dynamic transmission among intestinal helminths recorded in Yucatán, Mexico.


2001 ◽  
Vol 357 (2) ◽  
pp. 373-383 ◽  
Author(s):  
Timothy H. P. TAN ◽  
Steve A. V. EDGERTON ◽  
Rashmi KUMARI ◽  
Mark S. B. McALISTER ◽  
S. Mark ROWE ◽  
...  

cDNAs were obtained for macrophage migration-inhibitory factor (MIF)/l-dopachrome methyl ester tautomerase homologues from the parasitic nematodes Trichinella spiralis (TsMIF) and Trichuris trichiura (TtMIF). The translated sequences, which were partly confirmed by sequencing of proteolytic fragments, show 42 and 44% identity respectively with human or mouse MIF, and are shorter by one C-terminal residue. Unlike vertebrate MIF and MIF homologues of filarial nematodes, neither TsMIF nor TtMIF contain cysteine residues. Soluble recombinant TsMIF, expressed in Escherichia coli showed secondary structure (by CD spectroscopy) and quaternary structure (by light-scattering and gel filtration) similar to that of the trimeric mammalian MIFs and d-dopachrome tautomerase. The catalytic specificity of recombinant TsMIF in the ketonization of phenylpyruvate (1.4×106M−1·s−1) was comparable with that of human MIF, while that of p-hydroxyphenylpyruvate (9.1×104M−1·s−1) was 71-fold lower. TsMIF showed high specificity in tautomerization of the methyl ester of l-dopachrome compared with non-esterified l-dopachrome (>87000-fold) and a high kcat (≈ 4×104s−1). The crystal structure, determined to 1.65 Å (1 Å = 0.1nm), was generally similar to that of human MIF, but differed in the boundaries of the putative active-site pocket, which can explain the low activity towards p-hydroxyphenylpyruvate. The central pore was blocked, but was continuous, with the three putative tautomerase sites. Recombinant TsMIF (5ng/ml–5pg/ml) inhibited migration of human peripheral-blood mononuclear cells in a manner similar to that shown by human MIF, but had no effect from 5 to 500ng/ml on anti-CD3-stimulated murine T-cell proliferation. TsMIF was detected in supernatants of T. spiralis larvae cultured in vitro at 6ng/ml (55ng/mg total secreted protein). In conclusion TsMIF has structural, catalytic and cell-migration-inhibitory properties which indicate that it is partially orthologous to mammalian MIF.


2011 ◽  
Vol 208 (5) ◽  
pp. 893-900 ◽  
Author(s):  
Sumaira Z. Hasnain ◽  
Christopher M. Evans ◽  
Michelle Roy ◽  
Amanda L. Gallagher ◽  
Kristen N. Kindrachuk ◽  
...  

De novo expression of Muc5ac, a mucin not normally expressed in the intestinal tract, is induced in the cecum of mice resistant to Trichuris muris infection. In this study, we investigated the role of Muc5ac, which is detected shortly before worm expulsion and is associated with the production of interleukin-13 (IL-13), in resistance to this nematode. Muc5ac-deficient mice were incapable of expelling T. muris from the intestine and harbored long-term chronic infections, despite developing strong TH2 responses. Muc5ac-deficient mice had elevated levels of IL-13 and, surprisingly, an increase in the TH1 cytokine IFN-γ. Because TH1 inflammation is thought to favor chronic nematode infection, IFN-γ was neutralized in vivo, resulting in an even stronger TH2-type immune response. Nevertheless, despite a more robust TH2 effector response, the Muc5ac-deficient mice remained highly susceptible to chronic T. muris infection. Importantly, human MUC5AC had a direct detrimental effect on nematode vitality. Moreover, the absence of Muc5ac caused a significant delay in the expulsion of two other gut-dwelling nematodes (Trichinella spiralis and Nippostrongylus brasiliensis). Thus, for the first time, we identify a single mucin, Muc5ac, as a direct and critical mediator of resistance during intestinal nematode infection.


Parasitology ◽  
1997 ◽  
Vol 114 (1) ◽  
pp. 71-77 ◽  
Author(s):  
J. MODHA ◽  
M. C. ROBERTS ◽  
M. W. KENNEDY ◽  
J. R. KUSEL

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.


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