scholarly journals Chronic Intestinal Nematode Infection Exacerbates Experimental Schistosoma mansoni Infection

2008 ◽  
Vol 76 (12) ◽  
pp. 5802-5809 ◽  
Author(s):  
Quentin D. Bickle ◽  
Julie Solum ◽  
Helena Helmby
Keyword(s):  
Immune Response ◽  
Schistosoma Mansoni ◽  
Gastrointestinal Nematode ◽  
Nematode Infection ◽  
Portal System ◽  
Trichuris Muris ◽  
Intestinal Nematode ◽  
Parasite Infections ◽  
And Migration

ABSTRACT Mixed-parasite infections are common in many parts of the world, but little is known of the effects of concomitant parasite infections on the immune response or on disease progression. We have investigated the in vivo effects of a chronic gastrointestinal nematode infection on the infectivity and development of the immune response against the common trematode helminth Schistosoma mansoni. The data show that mice carrying an established chronic Trichuris muris infection and coinfected with S. mansoni, had significantly higher S. mansoni worm burdens than mice without coinfection. The increase in S. mansoni worm burden was accompanied by a higher egg burden in the liver. Kinetic analysis of S. mansoni establishment indicate reduced trapping of S. mansoni larvae during skin-to-lung migration, with T. muris-induced alterations in lung cytokine expression and inflammatory foci surrounding lung-stage schistosomula, suggesting that the immunomodulatory effects of chronic T. muris infection elicited at the gut mucosal surface extend to other organs and perhaps specifically to other mucosal surfaces. The data show that a preexisting chronic gastrointestinal nematode infection facilitates the survival and migration of S. mansoni schistosomula to the portal system, and as a result, increases the egg burden and associated pathology of S. mansoni infection.

Production of an interferon-gamma homologue by an intestinal nematode: functionally significant or interesting artefact?

Parasitology ◽  
1997 ◽  
Vol 115 (7) ◽  
pp. 101-105 ◽  
Author(s):  
R. K. GRENCIS ◽  
G. M. ENTWISTLE
Keyword(s):  
Immune Response ◽  
Host Immune Response ◽  
Interferon Γ ◽  
Host Immunity ◽  
Lymphoid Cells ◽  
Infectious Agents ◽  
Trichuris Muris ◽  
Intestinal Nematode ◽  
Induce Change

Chronic infection is a prominent feature of many intestinal nematode infections in man and animals. It is also clear that in such situations host immunity is activated but is unable to induce a protective response. A great deal of work has shown that genetic control of host immunity contributes to the variation in worm burdens often observed in the field. There is increasing appreciation, however, of the capability of infectious agents themselves to modulate the host immune response and potentiate their own survival. Using an immunologically well defined model of intestinal nematode infection in mice (Trichuris muris) we have shown that parasite derived molecules share cross reactive epitopes with the host cytokine interferon-γ using cytokine specific monoclonal antibodies in ELISA, Western blotting and immunoprecipitation assays. Furthermore, the parasite molecules can be shown to bind to the interferon-γ receptor and induce change in lymphoid cells similar to those induced by murine interferon-γ. The functional activity of the molecule in vivo remains to be determined. Previous studies have established that interferon-γ is critical for progression to chronic T. muris infection in mice and, therefore, it raises the distinct possibility that the production of an interferon-γ homologue by the worm may be one mechanism whereby the parasite is able to interfere with the regulation of the host immune response and potentiate its own survival.

scholarly journals Muc5ac: a critical component mediating the rejection of enteric nematodes

2011 ◽  
Vol 208 (5) ◽  
pp. 893-900 ◽  
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.

scholarly journals Intestinal Nematode Infection Ameliorates Experimental Colitis in Mice

2002 ◽  
Vol 70 (11) ◽  
pp. 5931-5937 ◽  
Author(s):  
W. I. Khan ◽  
P. A. Blennerhasset ◽  
A. K. Varghese ◽  
S. K. Chowdhury ◽  
P. Omsted ◽  
...  
Keyword(s):  
Immune Response ◽  
Trichinella Spiralis ◽  
Experimental Colitis ◽  
Developed Countries ◽  
Epidemiological Studies ◽  
Nematode Infection ◽  
Th2 Cells ◽  
Th2 Response ◽  
Th1 Cell ◽  
Intestinal Nematode

ABSTRACT Epidemiological studies suggest that inflammatory bowel disease (IBD) is common in developed countries and rare in countries where intestinal nematode infections are common. T cells are critical in many immune responses, including those associated with IBD and nematode infection. Among the distinct T helper (Th) cell subsets, Th1-type immune response is predominantly associated with Crohn's disease, while many nematode infections generate a strong Th2 response. The reciprocal cross regulation between Th1 and Th2 cells suggests that generation of a Th2 response by nematodes could prevent or reduce the effects of Th1-mediated diseases. In the present study, we investigated the effect of polarizing the immune response toward the Th2 type, using intestinal nematode infection, on subsequent experimental colitis. Mice were infected with the intestinal nematode Trichinella spiralis and allowed to recover before colitis was induced with dinitrobenzene sulfonic acid. The mice were sacrificed postcolitis to assess colonic damage macroscopically, histologically, and by myeloperoxidase (MPO) activity and Th cytokines. Prior nematode infection reduced the severity of colitis both macroscopically and histologically together with a decreased mortality and was correlated with a down-regulation of MPO activity, Th1-type cytokine expression in colonic tissue, and emergence of a Th2-type immune response. These results indicate a protective role of nematode infection in Th1 cell-driven inflammation and prompt consideration of a novel therapeutic strategy in IBD based on immunological distraction.

Schistosoma mansoni: structural damage and tegumental repair after in vivo treatment with praziquantel

Parasitology ◽  
1987 ◽  
Vol 94 (2) ◽  
pp. 243-254 ◽  
Author(s):  
M. K. Shaw ◽  
D. A. Erasmus
Keyword(s):  
Immune Response ◽  
Body Weight ◽  
Schistosoma Mansoni ◽  
Structural Damage ◽  
Post Treatment ◽  
Drug Induced ◽  
Male And Female ◽  
Extensive Damage

SUMMARYThe long-term, in vivo effects of a single, subcurative dose (200 mg/kg body weight of mouse) of praziquantel on the structure of adult Schistosoma mansoni and on the process and speed of tegumental repair are described. In both male and female worms praziquantel caused often extensive damage to the tegument, in the form of surface blebbings, swellings and lesions, and vacuolization and disruption of the subtegumental tissues. Repair of the drug-induced tegumental damage occurred slowly with partial and, more rarely, complete repair only being seen after 65 days post-treatment (p.t.), although signs of damage were still observed, particularly in male worms, at 100 days p.t. In contrast, repair of damage to the subtegumental/parenchymal tissues including the tegumental perikarya occurred relatively quickly, with the majority of worms examined appearing normal by 8–12 days p.t. The possible role(s) of the host immune response in relation to the speed of tegumental repair in vivo is discussed.

scholarly journals Identification of Novel Genes in Intestinal Tissue That Are Regulated after Infection with an Intestinal Nematode Parasite

2005 ◽  
Vol 73 (7) ◽  
pp. 4025-4033 ◽  
Author(s):  
R. Datta ◽  
M. L. deSchoolmeester ◽  
C. Hedeler ◽  
N. W. Paton ◽  
A. M. Brass ◽  
...  
Keyword(s):  
Trna Synthetase ◽  
Tryptophan Metabolism ◽  
Trichuris Muris ◽  
Local Responses ◽  
Intestinal Nematode ◽  
Expression Of Genes ◽  
Regulated Expression ◽  
Microarray Analyses

ABSTRACT Infection of resistant or susceptible mice with Trichuris muris provokes mesenteric lymph node responses which are polarized towards Th2 or Th1, respectively. These responses are well documented in the literature. In contrast, little is known about the local responses occurring within the infected intestine. Through microarray analyses, we demonstrate that the gene expression profile of infected gut tissue differs according to whether the parasite is expelled or not. Genes differentially regulated postinfection in resistant BALB/c mice include several antimicrobial genes, in particular, intelectin (Itln). In contrast, analyses in AKR mice which ultimately progress to chronic infection provide evidence for a Th1-dominated mucosa with up-regulated expression of genes regulated by gamma interferon. Increases in the expression of genes associated with tryptophan metabolism were also apparent with the coinduction of tryptophanyl tRNA synthetase (Wars) and indoleamine-2,3-dioxygenase (Indo). With the emerging literature on the role of these gene products in the suppression of T-cell responses in vitro and in vivo, their up-regulated expression here may suggest a role for tryptophan metabolism in the parasite survival strategy.

scholarly journals Interleukin (Il)-18 Promotes the Development of Chronic Gastrointestinal Helminth Infection by Downregulating IL-13

2001 ◽  
Vol 194 (3) ◽  
pp. 355-364 ◽  
Author(s):  
Helena Helmby ◽  
Kiyoshi Takeda ◽  
Shizuo Akira ◽  
Richard K. Grencis
Keyword(s):  
Critical Role ◽  
Gastrointestinal Nematode ◽  
Inhibitory Effect ◽  
Trichuris Muris ◽  
Gastrointestinal Helminth ◽  
Th Cell ◽  
Ifn Γ ◽  
In Vivo Treatment ◽  
Deficient Mice

Expulsion of the gastrointestinal nematode Trichuris muris is mediated by a T helper (Th) 2 type response involving interleukin (IL)-4 and IL-13. Here we show that Th1 response–associated susceptibility involves prior activation of IL-18 and caspase-1 followed by IL-12 and interferon (IFN)-γ in the intestine. IL-18–deficient mice are highly resistant to chronic T. muris infection and in vivo treatment of normal mice with recombinant (r)IL-18 suppresses IL-13 and IL-4 secretion but does not affect IFN-γ. In vivo treatment of T. muris–infected IFN-γ–deficient mice with rIL-18 demonstrated that the inhibitory effect of IL-18 on IL-13 secretion is independent of IFN-γ. Hence, IL-18 does not function as an IFN-γ–inducing cytokine during chronic T. muris infection but rather as a direct regulator of Th2 cytokines. These results provide the first demonstration of the critical role of IL-18 in regulating Th cell responses during gastrointestinal nematode infection.

Increased exposure of parasite antigens at the surface of adult male Schistosoma mansoni exposed to praziquantel in vitro

Parasitology ◽  
1986 ◽  
Vol 93 (2) ◽  
pp. 401-405 ◽  
Author(s):  
W. Harnett ◽  
J. R. Kusel
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Drug Treatment ◽  
Schistosoma Mansoni ◽  
Adult Male ◽  
Broad Spectrum ◽  
Host Immunity ◽  
Spastic Paralysis

SUMMARYPraziquantel is a broad-spectrum anthelmintic active against schistosome species which are major parasites of man. Two major effects on Schistosoma mansoni have been demonstrated; (i) spastic paralysis of the parasite musculature, possibly arising as a consequence of an influx of Ca2+ into the worm (Pax, Bennett & Fetterer, 1978; Coles, 1979) and (ii) vacuolation and degeneration of the worm tegument (Becker, Mehlhorn, Andrews, Thomas & Eckert, 1980). These events may contribute to the elimination of schistosomes in vivo, but this elimination may partly be dependent on the host immune response as infected T-cell-deprived mice are less able than immunologically intact animals to reduce their worm burdens following drug treatment (Doenhoff, Harrison, Sabah, Murare, Dunne & Hassounah, 1982). This latter observation raises the possibility that praziquantel may lower the ability of the parasite to evade host immunity by increasing the exposure of parasite antigens capable of acting as targets for host antibody, or antibody-armed cells at the worm surface. Consistent with this idea is the observation that adult schistosomes in praziquantel-treated mice are invaded a few hours after treatment by host granulocytes (Mehlhorn, Becker, Andrews, Thomas & Frenkel, 1981).

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