Epithelial cell apoptosis facilitates Entamoeba histolytica infection in the gut

Stephen M. Becker, Kyou Nam Cho, Xiaoti Guo, Kirsten Fendig, Mohammed N. Oosman, Robert Whitehead, Steven Cohn, Eric R. Houpt

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Entamoeba histolytica is the protozoan parasite that causes amebic colitis. The parasite triggers apoptosis on contact with host cells; however, the biological significance of this event during intestinal infection is unclear. We examined the role of apoptosis in a mouse model of intestinal amebiasis. Histopathology revealed that abundant epithelial cell apoptosis occurred in the vicinity of amoeba in histological specimens. Epithelial cell apoptosis occurred rapidly on co-culture with amoeba in vitro as measured by annexin positivity, DNA degradation, and mitochondrial dysfunction. Administration of the pan caspase inhibitor ZVAD decreased the rate and severity of amebic infection in CBA mice by all measures (cecal culture positivity , parasite enzyme-linked immunosorbent assay, and histological scores). Similarly, caspase 3 knockout mice on the resistant C57BL/6 background exhibited even lower cecal parasite antigen burden and culture positive rates than wild type mice. The permissive effect of apoptosis on infection could be tracked to the epithelium, in that transgenic mice that overexpressed Bcl-2 in epithelial cells were more resistant to infection as measured by cecal parasite enzyme-linked immunosorbent assay and histological scores. We concluded that epithelial cell apoptosis in the intestine facilitates amebic infection in this mouse model. The parasite's strategy for inducing apoptosis may point to key virulence factors, and therapeutic maneuvers to diminish epithelial apoptosis may be useful in amebic colitis.

Original languageEnglish (US)
Pages (from-to)1316-1322
Number of pages7
JournalAmerican Journal of Pathology
Volume176
Issue number3
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

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Entamoeba histolytica
Epithelial Cells
Apoptosis
Parasites
Amoebic Dysentery
Infection
Amoeba
Enzyme-Linked Immunosorbent Assay
Annexins
Inbred CBA Mouse
Caspase Inhibitors
Virulence Factors
Coculture Techniques
Mitochondrial DNA
Knockout Mice
Caspase 3
Transgenic Mice
Intestines
Epithelium
Antigens

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Becker, S. M., Cho, K. N., Guo, X., Fendig, K., Oosman, M. N., Whitehead, R., ... Houpt, E. R. (2010). Epithelial cell apoptosis facilitates Entamoeba histolytica infection in the gut. American Journal of Pathology, 176(3), 1316-1322. https://doi.org/10.2353/ajpath.2010.090740

Epithelial cell apoptosis facilitates Entamoeba histolytica infection in the gut. / Becker, Stephen M.; Cho, Kyou Nam; Guo, Xiaoti; Fendig, Kirsten; Oosman, Mohammed N.; Whitehead, Robert; Cohn, Steven; Houpt, Eric R.

In: American Journal of Pathology, Vol. 176, No. 3, 01.01.2010, p. 1316-1322.

Research output: Contribution to journalArticle

Becker, SM, Cho, KN, Guo, X, Fendig, K, Oosman, MN, Whitehead, R, Cohn, S & Houpt, ER 2010, 'Epithelial cell apoptosis facilitates Entamoeba histolytica infection in the gut', American Journal of Pathology, vol. 176, no. 3, pp. 1316-1322. https://doi.org/10.2353/ajpath.2010.090740
Becker, Stephen M. ; Cho, Kyou Nam ; Guo, Xiaoti ; Fendig, Kirsten ; Oosman, Mohammed N. ; Whitehead, Robert ; Cohn, Steven ; Houpt, Eric R. / Epithelial cell apoptosis facilitates Entamoeba histolytica infection in the gut. In: American Journal of Pathology. 2010 ; Vol. 176, No. 3. pp. 1316-1322.
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