Abstract:
:The protozoan parasite Entamoeba histolytica causes amebic dysentery and amebic liver abscess, diseases associated with significant morbidity and mortality worldwide. E. histolytica infection appears to involve the initial attachment of amebic trophozoites to intestinal epithelial cells, followed by lysis of these cells and subsequent invasion into the submucosa. A recent in vitro study (L. Eckmann, S. L. Reed, J. R. Smith, and M. F. Kagnoff, J. Clin. Invest. 96:1269-1279, 1995) demonstrated that incubation of E. histolytica trophozoites with epithelial cell lines results in epithelial cell production of inflammatory cytokines, including interleukin-1 (IL-1) and IL-8, suggesting that intestinal epithelial cell production of cytokines might play a role in the inflammatory response and tissue damage seen in intestinal amebiasis. To determine whether intestinal epithelial cell production of IL-1 and IL-8 occurs in response to E. histolytica infection in vivo and as an approach to studying the specific interactions between amebic trophozoites and human intestine, we used a SCID mouse-human intestinal xenograft (SCID-HU-INT) model of disease, where human intestinal xenografts were infected with virulent E. histolytica trophozoites. Infection of xenografts with E. histolytica trophozoites resulted in extensive tissue damage, which was associated with the development of an early inflammatory response composed primarily of neutrophils. Using oligonucleotide primers that specifically amplify human IL-1beta and IL-8, we could demonstrate by reverse transcription PCR that mRNA for both IL-1beta and IL-8 is produced by human intestinal xenografts in response to amebic infection. The increase in human intestinal IL-1beta and IL-8 in response to invasive amebiasis was confirmed by enzyme-linked immunosorbent assays specific for human IL-1beta and IL-8. Using immunohistochemistry, we confirmed that human intestinal epithelial cells were the source of IL-8 in infected xenografts and established that IL-8 production can occur at sites distal to areas of intestinal mucosal damage. These results demonstrate that human intestinal epithelial cells can produce inflammatory cytokines in response to infection in vivo and establish the SCID-HU-INT model as a system for studying the interactions between E. histolytica and human intestine.
journal_name
Infect Immunjournal_title
Infection and immunityauthors
Seydel KB,Li E,Swanson PE,Stanley SL Jrdoi
10.1128/IAI.65.5.1631-1639.1997subject
Has Abstractpub_date
1997-05-01 00:00:00pages
1631-9issue
5eissn
0019-9567issn
1098-5522journal_volume
65pub_type
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journal_title:Infection and immunity
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doi:10.1128/IAI.25.3.1075-1077.1979
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doi:10.1128/IAI.10.1.1-5.1974
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doi:10.1128/IAI.27.3.707-713.1980
更新日期:1980-03-01 00:00:00
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pub_type: 杂志文章
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更新日期:1984-09-01 00:00:00
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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doi:10.1128/IAI.9.4.772-774.1974
更新日期:1974-04-01 00:00:00
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journal_title:Infection and immunity
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doi:10.1128/IAI.62.6.2639-2643.1994
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.9.5.815-820.1974
更新日期:1974-05-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/IAI.19.3.919-922.1978
更新日期:1978-03-01 00:00:00
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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journal_title:Infection and immunity
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journal_title:Infection and immunity
pub_type: 杂志文章
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