Host–parasite interactions in rodent nematode infections

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.

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.


Parasitology ◽  
1979 ◽  
Vol 78 (2) ◽  
pp. 121-130 ◽  
Author(s):  
M. W. Kennedy ◽  
D. Wakelin ◽  
Margaret M. Wilson

SUMMARYA technique for the transplantation of Trichinella spiralis worms directly into the host intestine is described. Infections established by the direct transfer of adult worms were essentially normal both in terms of their survival and reproduction and in their stimulation of, and susceptibility to, host immune responses. Worms transplanted from NIH mouse donors at intervals after infection had an equal ability to survive in the recipient, even when taken from the donor shortly before or during the process of worm expulsion, showing that expulsion does not require worms to be irreversibly damaged. It was noted, however, that after 7 days in the donor the ability of the worm to reproduce in the recipient was temporarily impaired.


2003 ◽  
Vol 71 (5) ◽  
pp. 2430-2438 ◽  
Author(s):  
W. I. Khan ◽  
M. Richard ◽  
H. Akiho ◽  
P. A. Blennerhasset ◽  
N. E. Humphreys ◽  
...  

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.


2001 ◽  
Vol 280 (4) ◽  
pp. G640-G648 ◽  
Author(s):  
Bruce A. Vallance ◽  
Patricia A. Blennerhassett ◽  
Jan D. Huizinga ◽  
Stephen M. Collins

In response to nematode infection, the host presumably attempts to create an unfavorable environment to prevent larval penetration of the host and to expedite parasite expulsion from the gut. In this study, we have used W/WVmice with or without mast cells after bone marrow reconstitution (BMR-W/WV) to examine the role of mast cells in the host response. W/WV, BMR-W/WV, and wild-type (+/+) mice were infected with Trichinella spiralis. Infected W/WVmice exhibited less tissue damage and experienced a delay in worm expulsion and a greater degree of larval penetration of the gut leading to encystment in skeletal muscle. Tissue injury was greater and worm expulsion was normalized in BMR-W/WVmice, but larval penetration remained unchanged. Spontaneous contractile activity of jejunal muscle was disrupted in W/WVmice, as was the contractile response to carbachol. These abnormalities were also present in BMR-W/WVmice. These results indicate that mast cells mediate tissue damage and contribute to the timely expulsion of nematodes from the gut during primary infection.


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 ◽  
1980 ◽  
Vol 81 (1) ◽  
pp. 17-26 ◽  
Author(s):  
B. Z. Ngwenya

SUMMARYLactating and nulliparous outbred Swiss (CF-1 strain) mice were infected at 12–16 weeks of age with Nippostrongylus brasiliensis or Trichinella spiralis. Lysophospholipase B levels in the intestinal tissue and faecal pellets were greatly depressed in infected lactating mice in contrast to infected nulliparous mice. Correlated with these depressions in lysophospholipase levels were markedly reduced numbers of bonemarrow eosinophils in infected lactating mice. Although the peak levels of lysophospholipase in the intestinal tissues occurred in both nulliparous and lactating mice by days 9 and 14 after infection with N. brasiliensis and T. spiralis, respectively, lactating mice had significantly lower lysophospholipase peak levels than nulliparous mice. The peak of luminal levels of the enzyme coincided with peak levels of the enzyme in the intestinal tissues and with theexpulsion of the majority of the worms from the small intestines of nulliparous mice. However, lactation delayed the temporal relation between the peak of lysophospholipase levels in the intestinal lumen and worm expulsion. These results suggest that lactation depressed the levels of the enzyme and interfered with its release into the intestinal lumen.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ariel Munitz ◽  
L. Edry-Botzer ◽  
M. Itan ◽  
R. Tur-Kaspa ◽  
D. Dicker ◽  
...  

AbstractDespite ongoing efforts to characterize the host response toward SARS-CoV-2, a major gap in our knowledge still exists regarding the magnitude and duration of the humoral response. Analysis of the antibody response in mild versus moderate/severe patients, using our new developed quantitative electrochemiluminescent assay for detecting IgM/IgA/IgG antibodies toward SARS-CoV-2 antigens, revealed a rapid onset of IgG/IgA antibodies, specifically in moderate/severe patients. IgM antibodies against the viral receptor binding domain, but not against nucleocapsid protein, were detected at early stages of the disease. Furthermore, we observed a marked reduction in IgM/IgA antibodies over-time. Adapting our assay for ACE2 binding-competition, demonstrated that the presence of potentially neutralizing antibodies is corelated with IgG/IgA. Finally, analysis of the cytokine profile in COVID-19 patients revealed unique correlation of an IL-12p70/IL33 and IgG seroconversion, which correlated with disease severity. In summary, our comprehensive analysis has major implications on the understanding and monitoring of SARS-CoV-2 infections.


Parasitology ◽  
2010 ◽  
Vol 138 (4) ◽  
pp. 463-471 ◽  
Author(s):  
ALEKSANDAR ZOCEVIC ◽  
PAULINE MACE ◽  
ISABELLE VALLEE ◽  
RADU BLAGA ◽  
MINGYUAN LIU ◽  
...  

SUMMARYThree expression cDNA libraries fromTrichinella spiralisworms 14 h, 20 h and 48 h post-infection (p.i.) were screened with serum from pigs experimentally infected with 20 000T. spiralismuscle larvae. Twenty-nine positive clones were isolated from the 14 h p.i. cDNA library, corresponding to 8 different genes. A putative excretory-secretory protein similar to that ofT. pseudospiraliswas identified. Three clones corresponded to aT. spiralisserine proteinase inhibitor known to be involved in diverse functions such as blood coagulation and modulation of inflammation. Screening of the 20 h p.i. cDNA library selected 167 positive clones representing 12 different sequences. The clone with the highest redundancy encoded a small polypeptide having no sequence identity with any known proteins fromTrichinellaor other organisms. Fourteen clones displayed sequence identity with the heat shock protein (HSP) 70. HSPs are produced as an adaptive response of the parasite to the hostile environment encountered in the host intestine but their mechanism of action is not yet well defined. From the 48 h p.i.T. spiraliscDNA library, 91 positive clones were identified representing 7 distinct sequences. Most of the positive clones showed high similarity with a member of a putativeT. spiralisserine protease family. This result is consistent with a possible major role for serine proteases during invasive stages ofTrichinellainfection and host-parasite interactions.


Parasitology ◽  
1975 ◽  
Vol 71 (2) ◽  
pp. 275-283 ◽  
Author(s):  
R. J. Love ◽  
Bridget M. Ogilvie ◽  
Diane J. McLaren

When adult Nippostrongylus brasiliensis were maintained in vitro they became damaged. Using the criteria of ultrastructural morphology, acetylcholinesterase isoenzyme pattern and the behaviour of the worms after transfer to a normal rat, this damage appeared to be similar to that produced by the in vivo action of antibodies.Antibodies were shown to be responsible for the anterior migration of adult worms which occurs during primary infections in mature rats and in the prolonged infections seen in lactating and immature rats.Antibody damaged worms and worms unaffected by antibodies were equally able to stimulate the immune response required for worm expulsion. Apparently antibody damage is not required for the initiation of the second immune component necessary for expulsion of this parasite.


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