Association between TNF-α and <em>Entamoeba histolytica</em> Diarrhea

Kristine Peterson

Jianfen Shu

Priya Duggal

Rashidul Haque

Dinesh Mondal

William Petri

Division of Infectious Disease and International Health, University of Virginia Health System, Charlottesville, Virginia; International Centre for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh; Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

*Address correspondence to Kristine M. Peterson, Division of Infectious Diseases, University of Virginia Health Systems, PO BOX 801337, Building MR4, Room 2115, 409 Lane Road, Charlottesville, VA. E-mail: ude.ainigriv@v5pmk

Received 2009 Aug 25; Accepted 2009 Dec 24.

Abstract

An association between tumor necrosis factor α (TNF-α) and Entamoeba histolytica diarrhea was assessed in a cohort of 138 non-related Bangladeshi children who have been prospectively followed since 2001. Peripheral blood mononuclear cells (PBMCs) obtained at study entry were purified, cultured, and stimulated with soluble amebic antigen before cytokine measurement from supernatant. Higher levels of TNF-α were associated with increased risk of first (P = 0.01) and recurrent E. histolytica-related diarrheal episodes (P = 0.005). Children who developed E. histolytica diarrhea had significantly higher TNF-α protein levels than those who experienced asymptomatic E. histolytica infection (P value = 0.027) or no infection (P value = 0.017). Microarray studies performed using RNA isolated from acute and convalescent whole blood and colon biopsy samples revealed higher but non-significant TNF-α messenger RNA (mRNA) levels in subjects with acute E. histolytica diarrhea compared with convalescence. We conclude that there is an association between higher TNF-α production and E. histolytica diarrhea.

Abstract

Acknowledgments

We thank the families in Mirpur, Dhaka Bangladesh for their participation in these studies. We also thank Pat Pramoonjago and Christopher A. Moskaluk for assistance with immunohistochemistry.

Acknowledgments

Footnotes

Financial support: This work is supported by NIH grant K08A1072470 to Kristine M. Peterson, grant AI043596 to William A. Petri, and in part by the intramural division of the National Human Genome Research Institute, NIH.

Authors' addresses: Kristine M. Peterson and William A. Petri Jr, Division of Infectious Diseases, University of Virginia Health Systems, Charlottesville, VA, E-mail: ude.ainigriv@v5pmk. Jianfen Shu, Division of Biostatistics and Epidemiology, Department of Public Health Services, University of Virginia, Charlotteville, VA. Priya Duggal, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. Rashidul Haque and Dinesh Mondal, International Centre for Diarrheal Disease Research, Dhaka Bangladesh, Dhaka, Bangladesh.

Footnotes

References

1. Stanley SL., Jr Amoebiasis. Lancet. 2003;361:1025–1034.[PubMed]
2. Amidou S, Obi L, Bessong P, Stroup S, Houpt E, Guerrant RPrevalence and species distribution of E. histolytica and E. dispar in the Venda Region, Limpopo, South Africa. Am J Trop Med Hyg. 2006;75:565–571.[PubMed][Google Scholar]
3. Mondal D, Petri WA, Jr, Sack RB, Haque R. Entamoeba histolytica-associated diarrheal illness is negatively associated with the growth of preschool children: evidence from a prospective study. Trans R Soc Trop Med Hyg. 2006;100:1032–1038.[PubMed]
4. Haque R, Mondal D, Shu J, Roy S, Kabir M, Davis AN, Duggal P, Petri WA., Jr Correlation of interferon-gamma production by peripheral blood mononulcear cells with childhood malnutrition and susceptibility to amebiasis. Am J Trop Med Hyg. 2007;76:340–344.[PubMed]
5. Haque R, Ibnekarim A, Sack B, Farr B, Ramakrishnan G, Petri WA., Jr Amebiasis and mucosal IgA antibody against the Entamoeba histolytica adherence lectin in Bangladeshi children. JID. 2001;183:1787–1793.[PubMed]
6. Acevedo JA, Pacheco-Yépez J, Serrano-Luna J, Espinosa-Cantellano M, Tsutsumi V, Shibayama MExperimental amebic liver abscess: in vivo localization of TNF-alpha. Arch Med Res. 2000;31((Suppl)):S98–S100.[PubMed][Google Scholar]
7. Blazquez S, Zimmer C, Guigon G, Olivo-Marin JC, Guillén N, Labruyère EHuman tumor necrosis factor is a chemoattractant for the parasite Entamoeba histolytica. Infect Immun. 2006;74:1407–1411.[Google Scholar]
8. Denis M, Chadee KHuman neutrophils activated by interferon-gamma and tumour necrosis factor-alpha kill Entamoeba histolytica trophozoites in vitro. J Leukoc Biol. 1989;46:270–274.[PubMed][Google Scholar]
9. Denis M, Chadee KCytokine activation of murine macrophages for in vitro killing of Entamoeba histolytica trophozoites. Infect Immun. 1989;57:1750–1756.[Google Scholar]
10. Lin JY, Chadee KMacrophage cytotoxicity against Entamoeba histolytica trophozoites is mediated by nitric oxide from L-arginine. J Immunol. 1992;148:3999–4005.[PubMed][Google Scholar]
11. Lin JY, Séguin R, Keller K, Chadee KTumor necrosis factor alpha augments nitric oxide-dependent macrophage cytotoxicity against Entamoeba histolytica by enhanced expression of the nitric oxide synthase gene. Infect Immun. 1994;62:1534–1541.[Google Scholar]
12. Séguin R, Mann BJ, Keller K, Chadee KThe tumor necrosis factor alpha-stimulating region of galactose-inhibitable lectin of Entamoeba histolytica activates gamma interferon-primed macrophages for amebicidal activity mediated by nitric oxide. Infect Immun. 1997;65:2522–2527.[Google Scholar]
13. Séguin R, Mann BJ, Keller K, Chadee KIdentification of the galactose-adherence lectin epitopes of Entamoeba histolytica that stimulate tumor necrosis factor-alpha production by macrophages. Proc Natl Acad Sci USA. 1995;92:12175–12179.[Google Scholar]
14. Wang W, Keller K, Chadee KModulation of tumor necrosis factor production by macrophages in Entamoeba histolytica infection. Infect Immun. 1992;60:3169–3174.[Google Scholar]
15. Zhang Z, Mahajan S, Zhang X, Stanley SL., Jr Tumor necrosis factor alpha is a key mediator of gut inflammation seen in amebic colitis in human intestine in the SCID mouse-human intestinal xenograft model of disease. Infect Immun. 2003;71:5355–5359.
16. Zhang Z, Stanley SL., Jr Stereotypic and specific elements of the human colonic response to Entamoeba histolytica and Shigella flexneri. Cell Microbiol. 2004;6:535–554.[PubMed]
17. Bazzoni F, Beutler BThe tumor necrosis factor ligand and receptor families. N Engl J Med. 1996;334:1717–1725.[PubMed][Google Scholar]
18. Ma TY, Iwamoto GK, Hoa NT, Akotia V, Pedram A, Boivin MA, Said HMTNF-alpha-induced increase in intestinal epithelial tight junction permeability requires NF-kappa B activation. Am J Physiol Gastrointest Liver Physiol. 2004;286:G367–G376.[PubMed][Google Scholar]
19. Rojas-Cartagena C, Flores I, Appleyard CBRole of tumor necrosis factor receptors in an animal model of acute colitis. Cytokine. 2005;32:85–93.[PubMed][Google Scholar]
20. Kuhbacher T, Fölsch URPractical guidelines for the treatment of inflammatory bowel disease. World J Gastroenterol. 2007;13:1149–1155.[Google Scholar]
21. Greenberg DE, Jiang ZD, Steffen R, Verenker MP, DuPont HLMarkers of inflammation in bacterial diarrhea among travelers, with a focus on enteroaggregative Escherichia coli pathogenicity. JID. 2002;185:944–949.[PubMed][Google Scholar]
22. Nicholls S, Stephens S, Braegger CP, Walker-Smith JA, MacDonald TTCytokines in stools of children with inflammatory bowel disease or infective diarrhoea. J Clin Pathol. 1993;46:757–760.[Google Scholar]
23. Lin D, Wei L, Yang I, Ying ZSemiparametric regression for the mean and rate functions of recurrent events. J R Stat Soc, B. 2000;62:711–730.[PubMed][Google Scholar]
24. Breese EJ, Michie CA, Nicholls SW, Murch SH, Williams CB, Domizio P, Walker-Smith JA, MacDonald TTTumor necrosis factor alpha-producing cells in the intestinal mucosa of children with inflammatory bowel disease. Gastroenterology. 1994;106:1455–1466.[PubMed][Google Scholar]
25. Komatsu M, Kobayashi D, Saito K, Furuya D, Yagihashi A, Araake H, Tsuji N, Sakamaki S, Niitsu Y, Watanabe NTumor necrosis factor-alpha in serum of patients with inflammatory bowel disease as measured by a highly sensitive immuno-PCR. Clin Chem. 2001;47:1297–1301.[PubMed][Google Scholar]
26. Meijer MJ, Mieremet-Ooms MA, van Hogezand RA, Lamers CB, Hommes DW, Verspaget HWRole of matrix metalloproteinase, tissue inhibitor of metalloproteinase and tumor necrosis factor-alpha single nucleotide gene polymorphisms in inflammatory bowel disease. World J Gastroenterol. 2007;13:2960–2966.[Google Scholar]
27. Pedersen G, Saermark T, Kirkegaard T, Brynskov JSpontaneous and cytokine induced expression and activity of matrix metalloproteinases in human colonic epithelium. Clin Exp Immunol. 2009;155:257–265.[Google Scholar]
28. Zhou L, Yan C, Gieling RG, Kida Y, Garner W, Li W, Han YPTumor necrosis factor-alpha induced expression of matrix metalloproteinase-9 through p21-activated kinase-1. BMC Immunol. 2009;10:15.[Google Scholar]