Biomedical subjects

Eric Houpt

Publications and source records attributed to Eric Houpt.

8 recordsLinked to original sources

PubMed2006

Resistance of C57BL/6 mice to amoebiasis is mediated by nonhemopoietic cells but requires hemopoietic IL-10 production.

Resistance to intestinal amoebiasis is mouse strain dependent. C57BL/6 (B6) mice clear Entamoeba histolytica within hours of challenge, whereas C3H and CBA strains are susceptible to infection and disease. In this study, we show using bone marrow (BM) chimeric mice that mouse strain-dependent resistance is mediated by nonhemopoietic cells; specifically, B6 BM --> CBA recipients remained susceptible as measured by amoeba score and culture, whereas CBA BM --> B6 recipients remained resistant. Interestingly, hemopoietic IL-10 was required for maintaining the resistance of B6 mice, in that B6 IL-10-deficient mice and IL-10(-/-) BM --> wild-type recipients, but not IL-10(+/+) BM --> IL-10(-/-) recipients, exhibited higher amoeba scores than their wild-type controls. Additionally, C57BL/10 IL-10(-/-)Rag2(-/-) mice exhibited diminished amoeba scores and culture rates vs IL-10(-/-) mice, indicating that lymphocytes potentiated the susceptibility of IL-10-deficient mice. We conclude that nonhemopoietic cells mediate the natural resistance to intestinal amoebiasis of B6 mice, yet this resistance depends on hemopoietic IL-10 activity.

Animals↗

PubMed2006

Impact of intestinal colonization and invasion on the Entamoeba histolytica transcriptome.

A genome-wide transcriptional analysis of Entamoeba histolytica was performed on trophozoites isolated from the colon of six infected mice and from in vitro culture. An Affymetrix platform gene expression array was designed for this analysis that included probe sets for 9435 open reading frames (ORFs) and 9066 5' and 3' flanking regions. Transcripts were detected for > 80% of all ORFs. A total of 523 transcripts (5.2% of all E. histolytica genes) were significantly changed in amebae isolated from the intestine on Days 1 and 29 after infection: 326 and 109 solely on Days 1 and 29, and 88 on both days. Quantitative real-time reverse transcriptase PCR confirmed these changes in 11/12 genes tested using mRNA isolated from an additional six mice. Adaptation to the intestinal environment was accompanied by increases in a subset of cell signaling genes including transmembrane kinases, ras and rho family GTPases, and calcium binding proteins. Significant decreases in mRNA abundance for genes involved in glycolysis and concomitant increases in lipases were consistent with a change in energy metabolism. Defense against bacteria present in the intestine (but lacking from in vitro culture) was suggested by alterations in mRNA levels of genes similar to the AIG1 plant antibacterial proteins. Decreases in oxygen detoxification pathways were observed as expected in the anaerobic colonic lumen. Of the known virulence factors the most remarkable changes were a 20-35-fold increase in a cysteine proteinase four-like gene, and a 2-3-fold decrease in two members of the Gal/GalNAc lectin light subunit family. Control of the observed changes in mRNA abundance in the intestine might potentially rest with four related proteins with DNA binding domains that were down-regulated 6-16-fold in the intestinal environment. In conclusion, the first genome-wide analysis of the transcriptome of E. histolytica demonstrated that the vast majority of genes are transcribed in trophozoites, and that in the host intestine trophozoites altered the expression of mRNAs for genes implicated in metabolism, oxygen defense, cell signaling, virulence, antibacterial activity, and DNA binding.

Animals↗

PubMed2006

Adherence-blocking vaccine for amebiasis.

The Gal/GalNAc lectin is a candidate vaccine antigen for an amebiasis vaccine due to its mediation of parasite adherence to the human intestine, because partial immunity in humans is associated with a mucosal IgA response against it, and because it is effective as a vaccine against amebic colitis in the murine model. The LecA domain of the Gal/GalNAc lectin contains neutralizing antibody epitopes. LecA contains the active site of the lectin (the carbohydrate recognition domain or "CRD") and has been an effective vaccine antigen in animal models of amebic colitis and liver abscess. Research needs include production of the LecA domain of the Gal/GalNAc lectin by a process that can be transferred to cGMP and optimization for immunogenicity, using adjuvants such as alum, MF59 or QS-21 adjuvants. Accomplishing this will enable testing of the ability of LecA immunizations to protect from amebic colitis in humans.

Animals↗

PubMed2006

Prevalence and species distribution of E. Histolytica and E. Dispar in the Venda region, Limpopo, South Africa.

The prevalence and species distribution of Entamoeba histolytica and E. dispar in the Venda region were determined in stool samples collected from public hospitals and primary schools by ELISA and a nested polymerase chain reaction (PCR). E. histolytica was detected in 37/197 (18.8%) and 1/47 (2.1%) samples, whereas 50/197 (25.3%) and 4/47 (8.5%) had E. dispar in the hospitals and schools, respectively. The age groups most infected were 0-2 (33%) years followed by 20-29 years (27%). E. histolytica was significantly associated with diarrhea (77.4% versus 22.6%; chi 2 = 39.48, P < 0.05), and with the presence of lactoferrin (85.7% versus 14.2%) in the stools, indicating intestinal inflammation (chi 2 = 29.605, P < 0.05). E. histolytica was found in 5 (16.12%) of the 31 HIV-positive individuals and in 33 (15.5%) of the 213 HIV-negative individuals. E. histolytica infections are common in the Venda region and are associated with diarrhea and intestinal inflammation.

Adolescent↗

PubMed2005

Global impact of diarrheal diseases that are sampled by travelers: the rest of the hippopotamus.

Travelers who experience diarrhea (i.e., "turista") are exposed to the same pathogens and illnesses that pose some of the greatest threats to life and development among malnourished children in developing areas around the world, where inadequate water and poor sanitation remain. This article focuses on new findings about the impact, diagnosis, and control of these illnesses and the genetic predispositions of persons who acquire them. Despite the reductions in mortality due to dehydrating diarrhea, the morbidity associated with diarrheal illnesses continues unabated. Furthermore, we increasingly recognize the lasting detrimental effects of enteric infections that occur during early childhood on later physical and cognitive development and, in patients with acquired immunodeficiency syndrome, on the absorption of antiretroviral drugs. Genetic predispositions to inflammation and potential protection associated with such alleles as ApoE4, which are not suspected of being involved in diarrhea, remind us of how much we have to learn about the effect and interactions of enteric tropical infectious diseases with regard to our host genome. New diagnostic methods hold promise for improved recognition and, hopefully, control of enteric infections worldwide.

Diarrhea↗

PubMed2005

Resistance to intestinal Entamoeba histolytica infection is conferred by innate immunity and Gr-1+ cells.

Establishment of intestinal infection with Entamoeba histolytica depends on the mouse strain; C57BL/6 mice are highly resistant, and C3H/HeJ mice are relatively susceptible. We found that resistance to intestinal infection was independent of lymphocyte activity or H-2 haplotype and occurred in the first hours to days postchallenge according to in vivo imaging. At 18 h postchallenge, the ceca of resistant C57BL/6 mice were histologically unremarkable, in contrast to the severe inflammation observed in susceptible C3H/HeJ mice. Comparison of cecal gene expression in C3H/HeJ and C57BL/6 mice demonstrated that there was parasite-induced upregulation of proinflammatory and neutrophil chemotaxis transcripts and there was downregulation of transforming growth factor beta signaling molecules. Pretreatment with dexamethasone abrogated the partial resistance of C3H/HeJ or CBA mice through an innate, lymphocyte-independent mechanism, but it had no effect on the high-level resistance of C57BL/6 mice. Similarly, administration of a neutrophil-depleting anti-Gr-1 monoclonal antibody (RB6-8C5) decreased the partial resistance of CBA mice and led to severe pathology compared to control antibody-treated mice, but it had no effect on C57BL/6 resistance. These data indicate that there are discrete mechanisms of innate resistance to E. histolytica depending on the host background and, in contrast to other reports, imply that neutrophils are protective and not damaging in intestinal amebiasis.

Animals↗

PubMed2004

Prevention of intestinal amebiasis by vaccination with the Entamoeba histolytica Gal/GalNac lectin.

Prevention of intestinal infection by Entamoeba histolytica would block both invasive disease and parasite transmission. The amebic Gal/GalNAc lectin mediates parasite adherence to the colonic surface and fecal anti-lectin IgA is associated with protection from intestinal reinfection in children. We tested if vaccination with the E. histolytica Gal/GalNAc lectin could prevent cecal infection in a C3H mouse model of amebic colitis. Two trials using native lectin purified from the parasite and two trials using a 64 kDa recombinant fragment ("LecA") were performed with a combined intranasal and intraperitoneal immunization regimen using cholera toxin and Freund's adjuvants, respectively. Two weeks after immunization mice were challenged intracecally with trophozoites, and 4-12 weeks after challenge mice were sacrificed for histopathologic evaluation of infection. Vaccination prevented intestinal infection with efficacies of 84 and 100% in the two native lectin trials and 91 and 34% in the two LecA trials. Mice with detectable pre-challenge fecal anti-lectin IgA responses were significantly more resistant to infection than mice without fecal anti-lectin IgA responses. These results show for the first time that immunization with the Gal/GalNAc lectin can prevent intestinal amebiasis in mice and suggest a protective role for fecal anti-lectin IgA in vivo.

Administration, Intranasal↗

PubMed2003

Amebiasis.

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Amebicides↗