Screening of Capillaria philippinensis infection using Trichuris muris and Trichinella spiralis antigens

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.

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Specific cross-immunity between Trichinella spiralis and Trichuris muris: immunization with heterologous infections and antigens and transfer of immunity with heterologous immune mesenteric lymph node cells

Parasitology ◽

10.1017/s0031182000044929 ◽

1982 ◽

Vol 84 (2) ◽

pp. 381-389 ◽

Cited By ~ 27

Author(s):

T. D. G. Lee ◽

R. K. Grencis ◽

D. Wakelin

Keyword(s):

Lymph Node ◽

Mesenteric Lymph Node ◽

Primary Infection ◽

Trichinella Spiralis ◽

The Other ◽

Trichuris Muris ◽

Mesenteric Lymph ◽

Heterologous Challenge ◽

Lymph Node Cells ◽

Cross Immunity

SUMMARYInfections with either 300 infective Trichinella spiralis larvae or 400 embryonated eggs of Trichuris muris were effective in eliciting accelerated expulsion of heterologous challenge infections given 20 days after the primary infection. Accelerated expulsion could also be achieved by the administration of soluble crude worm antigen given 12 days prior to heterologous challenge or by adoptive transfer of mesenteric lymph node cells taken from mice infected with the heterologous parasite. Each species is capable of eliciting an accelerated secondary expulsion response in hosts that have been actively or adoptively immunized against the other species and these results are taken to indicate that there is a specific cross-immunity between T. spiralis and T. muris due to shared antigens. It is postulated that these shared antigens are derived from stichocyte granules.

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

Biochemical Journal ◽

10.1042/bj3350495 ◽

1998 ◽

Vol 335 (3) ◽

pp. 495-498 ◽

Cited By ~ 31

Author(s):

Joanne L. PENNOCK ◽

Jerzy M. BEHNKE ◽

Quentin D. BICKLE ◽

Eileen DEVANEY ◽

Richard K. GRENCIS ◽

...

Keyword(s):

Methyl Ester ◽

Soluble Fraction ◽

Trichinella Spiralis ◽

Hymenolepis Diminuta ◽

Nippostrongylus Brasiliensis ◽

Macrophage Migration ◽

Trichuris Muris ◽

Brugia Pahangi ◽

Dopachrome Tautomerase ◽

Parasitic Helminths

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.

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Antigenic cross-reactivity between the human whipworm, Trichuris trichiura, and the mouse trichuroids Trichuris muris and Trichinella spiralis

Parasite Immunology ◽

10.1111/j.1365-3024.1988.tb00221.x ◽

1988 ◽

Vol 10 (3) ◽

pp. 279-291 ◽

Cited By ~ 38

Author(s):

T.I.A. Roach ◽

D. Wakelin ◽

K.J. Else ◽

D.A.P. Bundy

Keyword(s):

Trichinella Spiralis ◽

Cross Reactivity ◽

Trichuris Trichiura ◽

Trichuris Muris

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Contrasting effects of Trichinella spiralis and Trichuris muris antigens on the infection by Leishmania infantum in BALB/c mice

Acta Tropica ◽

10.1016/j.actatropica.2007.06.008 ◽

2007 ◽

Vol 103 (3) ◽

pp. 212-221 ◽

Cited By ~ 3

Author(s):

M.A. Dea-Ayuela ◽

S. Rama-Iñiguez ◽

F. Bolas-Fernández

Keyword(s):

Leishmania Infantum ◽

Trichinella Spiralis ◽

Trichuris Muris

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Immunological interactions between Trichinella spiralis and Trichuris muris in the intestine of the mouse

Parasitology ◽

10.1017/s003118200004765x ◽

1977 ◽

Vol 74 (2) ◽

pp. 163-173 ◽

Cited By ~ 24

Author(s):

R. G. Burce ◽

D. Wakelin

Keyword(s):

Small Intestine ◽

T Cell ◽

Inflammatory Response ◽

Large Intestine ◽

Trichinella Spiralis ◽

The Other ◽

Trichuris Muris ◽

Immunological Interactions ◽

Concurrent Infections ◽

Cross Immunity

In outbred (CFLP) and inbred (NIH) mice, the inflammatory response which is thought to be party responsible for the expulsion of Trichinella spiralis from the mid-region of the small intestine, also seemed to be largely responsible fo rthe simulataneous (i.e. early) expulsion of Trichuris muris from the caecum and large intestine during concurrent primary infections. The intractive explusion operated only when the concurrent infections were timed to produce T. Spiralis expulsion before T. muris expulsion would normally occur and the effect persisted for several days after T. Spiralis has been expelled.Interactive expulsion wasss depressed during application of the nonsteroid, anti-inflammatory drug indomethacin and by T-cell expulsion of T. spiralis. These results indicate that a T-cell mediated inflammatory response was probably the basis of the interaction.When the timing of the infections was altered such that the expulsion of T. spiralis there was no reciprocal ecpulsion of the latter. Mice immunized againest one or the other species did not show cross-immunity on heterologus challenge, confirming that the interaction did not involve similar antigens in the two species. The interactive expulsive response is considered as an example of an indirect cross-immunity.

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Interleukin-9 Enhances Resistance to the Intestinal Nematode Trichuris muris

Infection and Immunity ◽

10.1128/iai.66.8.3832-3840.1998 ◽

1998 ◽

Vol 66 (8) ◽

pp. 3832-3840 ◽

Cited By ~ 101

Author(s):

Helen Faulkner ◽

J.-C. Renauld ◽

J. Van Snick ◽

R. K. Grencis

Keyword(s):

Immune Response ◽

Immunoglobulin E ◽

Trichinella Spiralis ◽

Inbred Strains ◽

Response Characteristic ◽

Interleukin 4 ◽

Mouse Strains ◽

Trichuris Muris ◽

Type Response

ABSTRACT Upon infection with the cecum-dwelling nematode Trichuris muris, the majority of inbred strains of mice launch a Th2-type immune response and in doing so expel the parasite before patency. In contrast, there are a few mouse strains which develop a nonprotective Th1-type response resulting in a chronic infection and the presence of adult worms. Of the Th2 cytokines known to be associated with the resistant phenotype (interleukin-4 [IL-4], IL-5, IL-9, and IL-13), comparatively little is known about the contribution that IL-9 makes towards the protective immune response. In this study we demonstrate that IL-9 is expressed early during the Th2-type response and that its elevation in vivo results in the enhancement of intestinal mastocytosis and the production of both the immunoglobulin E (IgE) and IgG1 isotypes. In addition, elevated IL-9 levels in vivo facilitated the loss of T. muris from the intestine. That IL-9 is important in promoting worm expulsion was also seen following infection of IL-9-transgenic mice, which constitutively overexpress the cytokine. These animals displayed an extremely rapid, but immune mediated, expulsion of the parasite. Also evident in these animals was a pronounced intestinal mastocytosis, which was previously shown by us to be responsible for the expulsion of the related nematodeTrichinella spiralis from these animals. Taken together with observations of IL-9 production following infection with other helminths, the results imply that IL-9 contributes to the general mast cell and IgE response characteristic of these infections and, more specifically, enhances resistance to T. muris.

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Modulation of Intestinal Muscle Contraction by Interleukin-9 (IL-9) or IL-9 Neutralization: Correlation with Worm Expulsion in Murine Nematode Infections

Infection and Immunity ◽

10.1128/iai.71.5.2430-2438.2003 ◽

2003 ◽

Vol 71 (5) ◽

pp. 2430-2438 ◽

Cited By ~ 97

Author(s):

W. I. Khan ◽

M. Richard ◽

H. Akiho ◽

P. A. Blennerhasset ◽

N. E. Humphreys ◽

...

Keyword(s):

Muscle Contraction ◽

Trichinella Spiralis ◽

Th2 Cells ◽

Mucosal Mast Cell ◽

Cell Hyperplasia ◽

Trichuris Muris ◽

Intestinal Nematode ◽

Worm Expulsion ◽

Interleukin 9

ABSTRACT Immune responses associated with intestinal nematode infections are characterized by the activation of T-helper 2 (Th2) cells. Previous studies demonstrated that during Trichinella spiralis infection, Th2 cells contribute to the development of intestinal muscle hypercontractility and to worm eviction from the gut, in part through signal transducer and activator of transcription factor 6 (Stat6). Interleukin-9 (IL-9), a Th2-cell-derived cytokine, has pleiotropic activities on various cells that are not mediated through Stat6. In this study, we investigated the role of IL-9 in the generation of enteric muscle hypercontractility in mice infected with the intestinal parasite T. spiralis and the cecal parasite Trichuris muris. Treatment of mice with IL-9 enhanced infection-induced jejunal muscle hypercontractility and accelerated worm expulsion in T. spiralis infection. These effects were associated with an up-regulation of IL-4 and IL-13 production from in vitro-stimulated spleen cells. In addition, increases in the level of intestinal goblet cells and in the level of mouse mucosal mast cell protease 1 (MMCP-1) in serum were observed in infected mice following IL-9 administration. However, the neutralization of IL-9 by anti-IL-9 vaccination or by anti-IL-9 antibody had no significant effect on worm expulsion or muscle contraction in T. spiralis-infected mice. In contrast, the neutralization of IL-9 significantly attenuated T. muris infection-induced colonic muscle hypercontractility and inhibited worm expulsion. The attenuated expulsion of the parasite by IL-9 neutralization was not accompanied by changes in goblet cell hyperplasia or the MMCP-1 level. These findings suggest that IL-9 contributes to intestinal muscle function and to host protective immunity and that its importance and contribution may differ depending on the type of nematode infection.

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Muc5ac: a critical component mediating the rejection of enteric nematodes

Journal of Experimental Medicine ◽

10.1084/jem.20102057 ◽

2011 ◽

Vol 208 (5) ◽

pp. 893-900 ◽

Cited By ~ 172

Author(s):

Sumaira Z. Hasnain ◽

Christopher M. Evans ◽

Michelle Roy ◽

Amanda L. Gallagher ◽

Kristen N. Kindrachuk ◽

...

Keyword(s):

De Novo ◽

Trichinella Spiralis ◽

Nematode Infection ◽

Nippostrongylus Brasiliensis ◽

Chronic Infections ◽

Trichuris Muris ◽

Intestinal Nematode ◽

Ifn Γ ◽

Deficient Mice

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.

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The protease phenotype and crystalline nature of the granules of intraepithelial mast cells in Trichinella spiralis-infected mice

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100140464 ◽

1995 ◽

Vol 53 ◽

pp. 818-819

Author(s):

D.S. Friend ◽

N. Ghildyal ◽

M.F. Gurish ◽

K.F. Austen ◽

R.L. Stevens

Keyword(s):

Small Intestine ◽

Mast Cells ◽

Epithelial Cells ◽

Lamina Propria ◽

Trichinella Spiralis ◽

Intestinal Epithelial ◽

Carboxypeptidase A ◽

C3h Mice ◽

Granule Morphology ◽

Crystalline Nature

Trichinella spiralis induces a profound mastocytosis and eosinophilia in the small intestine of the infected mouse. Mouse mast cells (MC) store in their granules various combinations of at least five chymotryptic chymases [designated mouse MC protease (mMCP) 1 to 5], two tryptic proteases designated mMCP-6 and mMCP-7 and an exopeptidase, carboxypeptidase A (mMC-CPA). Using antipeptide, protease -specific antibodies to these MC granule proteases, immunohistochemistry was done to determine the distribution, number and protease phenotype of the MCs in the small intestine and spleen 10 to >60 days after Trichinella infection of BALB/c and C3H mice. TEM was performed to evaluate the granule morphology of the MCs between intestinal epithelial cells and in the lamina propria (mucosal MCs) and in the submucosa, muscle and serosa of the intestine (submucosal MCs).As noted in the table below, the number of submucosal MCs remained constant throughout the study. In contrast, on day 14, the number of MCs in the mucosa increased ~25 fold. Increased numbers of MCs were observed between epithelial cells in the mucosal crypts, in the lamina propria and to a lesser extent, between epithelial cells of the intestinal villi.

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