Skip to main content
Log in

Immunopathological assessments of human Blastocystis spp. in experimentally infected immunocompetent and immunosuppresed mice

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

Blastocystis spp., one of the most common parasites colonizing the human intestine, is an extracellular, luminal protozoan with controversial pathogenesis. The host’s immune response against Blastocystis spp. infection has also not been defined yet. Therefore, this research aimed to assess the potential pathogenicity of this parasite and its ability to modulate the immune response in experimental infected immunocompetent and immunosuppresed mice. These results demonstrated that the infected immunosuppressed mice were more affected than infected immunocompetent mice. Histopathological examination of the small intestine in the infected immunosuppressed mice showed that Blastocystis spp. infiltrated all the layers. Moreover, the epithelia showed exfoliation and inflammatory cell infiltration in submucosa compared to that of the infected immunocompetent mice. As well, examination of the large intestine of the infected immunosuppressed group showed severe goblet cell hyperplasia. Blastocystis spp. infiltrated all the large intestine layers compared to that of the infected immunocompetent group. Furthermore, there was a significant upregulation of the expression of proinflammatory cytokines: interleukin 12 (IL-12) and tumor necrosis factor alpha (TNF-α) in the infected immunosuppressed mice compared to that of the infected immunocompetent ones (p ≤ 0.004 and p ≤ 0.002, respectively). However, the expression of anti-inflammatory cytokines (IL-4 and IL-10) was significantly downregulated in the infected immunosuppressed group compared to that of the infected immunocompetent group one at 10 days postinfection (p ≤ 0.002 and p ≤ 0.001, respectively). The results of this study revealed that Blastocystis spp. affected the production of pro- and anti-inflammatory cytokines in both groups of mice compared to healthy normal (naive) group. Additionally, these data showed that there was a significant upregulation (p ≤ 0.005) of the locally synthesized antibody: secretary IgA (sIgA) in the gut of the infected immunocompetent mice when compared to that of the infected immunosuppressed ones.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Abdel-Hafeez EH, Ahmed AK, Abdelgelil NH, Abdellatif MZM, Kamal AM, Mohamed RM (2015) In-vitro effect of some Egyptian herbal extracts against Blastocystis spp. J Egypt Soc Parasitol 45:93–100

    Article  PubMed  Google Scholar 

  • Abou-El Naga I, Negm A (2001) Morphology, histochemistry and infectivity of Blastocystis hominis cysts. J Egypt Soc Parasitol 31:627–635

    CAS  PubMed  Google Scholar 

  • Al-kaissi E, Al-Magdi KJ (2009) Pathogenicity of Blastocystis hominis in Relation to Entropathogens in Gastroenteritis Cases in Baghdad. Eur J Sci Res 25:606–613

    Google Scholar 

  • Bancroft JD, Gamble A (2008) Theory and practice of Histological techniques. 6th Ed., Churchill-Livingstone, Edinburgh, London, Melbourne, New York

  • Boorom KF, Smith H, Nimri I, Viscogliosi E, Spanakos G, Parkar U (2008) Oh my aching gut: Irritable bowel syndrome, Blastocystis and asymptomatic infection. Parasit Vectors 1(1):40. doi:10.1186/1756-3305-1-40

  • Boshuizen JA, Reimerink JH, Korteland-van Male AM, van Ham VJ, Bouma J, Gerwig GJ, Koopmans MP, Büller HA, Dekker J, Einerhand AW (2005) Homeostasis and function of goblet cells during rotavirus infection in mice. Virol J 337:210–221

    Article  CAS  Google Scholar 

  • Chandramathi S, Suresh KG, Mahmood AA, Kuppusamy UR (2010) Urinary hyaluronidase activity in rats infected with Blastocystis hominis—evidence for invasion? Parasitol Res 106:1459–1463

    Article  CAS  PubMed  Google Scholar 

  • Chen TL, Chan CC, Chen HP, Fung CP, Lin CP, Chan WL, Liu CY (2003) Clinical characteristics and endoscopic findings associated with Blastocystis hominis in healthy adults. Am J Trop Med Hyg 69:213–216

    PubMed  Google Scholar 

  • Dogruman ALF, Hokelek M (2007) Blastocystis hominis is an opportunistic pathogen. Turk J Parasitol 31:28–36

    Google Scholar 

  • Dogruman ALF, Simsek Z, Boorom K, Ekici E, Sahin M, Tuncer C, Kustimur S, Altinbas A (2010) Comparison of methods for detection of Blastocystis infection in routinely submitted stool samples, and also in IBS/IBD Patients in Ankara, Turkey. PLoS One 5:e15484

    Article  Google Scholar 

  • El-Gebaly NSM, Zaki MM (2012) Ultrastuctural intestinal pathology induced by human Blastocystis in experimentally infected mice. P U J 5:127–134

    Google Scholar 

  • Elwakil HS, Hewedi IH (2010) Pathogenic potential of Blastocystis hominis in laboratory mice. Parasitol Res 107:685–9

    Article  PubMed  Google Scholar 

  • Fayer R, Esposito DH, Dubey JP (2015) Human infections with Sarcocystis species. Clin Microbiol Rev 28:295–311

    Article  PubMed  PubMed Central  Google Scholar 

  • Fouad SA, Basyoni MM, Fahmy RA, Kobaisi MH (2011) The pathogenic role of different Blastocystis hominis genotypes isolated from patients with irritable bowel syndrome. Arab J Gastroenterol 12:194–200

    Article  PubMed  Google Scholar 

  • Garavelli PL, Orsi P, Scaglione L (1988) Blastocystis hominis infection during AIDS. Lancet 332:1364

    Article  Google Scholar 

  • Garavelli PL, Scaglione L, Bicocchi R, Libanore M (1991) Pathogenicity of Blastocystis hominis. Infection 19:185

    Article  CAS  PubMed  Google Scholar 

  • Garcia LS (2001) Diagnostic Medical Parasitology, 4th edn. ASM Press, Washington DC, USA, pp 87–97

    Google Scholar 

  • Hansson GC (2012) Role of mucus layers in gut infection and inflammation. Curr Opin Microbiol 15:57–62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hussein EM, Hussein AM, Eida MM, Atwa MM (2008) Pathophysiological variability of different genotypes of human Blastocystis hominis Egyptian isolates in experimentally infected rats. Parasitol Res 102:853–860

    Article  PubMed  Google Scholar 

  • Iguchi A, Yoshikawa H, Yamada M, Kimata I, Arizono N (2009) Expression of interferon gamma and proinflammatory cytokines in the cecal mucosa of rats experimentally infected with Blastocystis spp. strain RN94-9. Parasitol Res 105:135–140

    Article  PubMed  Google Scholar 

  • Khan WI (2008) Physiological changes in the gastrointestinal tract and host protective immunity: learning from the mouse-Trichinella spiralis model. Parasitolo 135:671–682

    Article  CAS  Google Scholar 

  • Leder K, Hellard ME, Sinclair MI, Fairley CK, Wolfe R (2005) No correlation between clinical symptoms and Blastocystis hominis in immunocompetent individuals. J Gastroenterol Hepatol 20:1390–1394

    Article  PubMed  Google Scholar 

  • Mahmoud MS, Saleh WA (2003) Secretory and humoral antibody responses to Blastocystis hominis in symptomatic and asymptomatic human infections. J Egypt Soc Parasitol 33:13–30

    PubMed  Google Scholar 

  • McDole JR, Wheeler LW, McDonald KG, Wang B, Konjufca V, Knoop KA, Newberry RD, Miller MJ (2012) Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine. Nature 483:345–349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller HR (1987) Gastrointestinal mucus, a medium for survival and for elimination of parasitic nematodes and protozoa. Parasitolo 94:77–100

    Article  Google Scholar 

  • Miné JC, Rosa JA (2008) Frequency of Blastocystis spp. hominis and other intestinal parasites in stool samples examined at the Parasitology Laboratory of the School of Pharmaceutical Sciences at the São Paulo State University, Araraquara. Rev Soc Bras Med Trop 41:565–569

    Article  PubMed  Google Scholar 

  • Mirza H, Wu Z, Teo JD, Tan KS (2012) Statin-pleiotropy prevents rho kinase-mediated intestinal epithelial barrier compromise induced by Blastocystis cysteineproteases. Cell Microbiol 14:1474–1484

    Article  CAS  PubMed  Google Scholar 

  • Moe KT, Singh M, Howe J, Ho LC, Tan SW, Chen XQ, Ng GC, Yap EH (1997) Experimental Blastocystis hominis infection in laboratory mice. Parasitol Res 83:319–325

    Article  CAS  PubMed  Google Scholar 

  • Nagel R, Bielefeldt-Ohmann H, Traub R (2014) Clinical pilot study: efficacy of triple antibiotic therapy in Blastocystis positive irritable bowel syndrome patients. Gut Pathogens 6:1–9

    Article  Google Scholar 

  • Poirier PH, Wawrzyniak I, Vivare’ CP, Delbac F, El Alaoui H (2012) New insights into Blastocystis spp.: a potential link with irritable bowel syndrome. Plos Pathog 8:1–4

    Article  Google Scholar 

  • Ponce-Macotela M, González-Maciel A, Reynoso-Robles R, Martínez-Gordillo MN (2008) Goblet cells: are they an unspecific barrier against Giardia intestinalis or a gate? Parasitol Res 102:509–513

    Article  PubMed  Google Scholar 

  • Puthia M, Vaithilingam A, Lu J, Tan K (2005) Degradation of human secretory immunoglobulin A by Blastocystis. Parasitol Res 97:286–289

    Article  Google Scholar 

  • Rossignol JF, Kabil SM, Said M, Samir H, Younis AM (2005) Effect of nitazoxanide in persistent diarrhea and enteritis associated with Blastocystis hominis. Clin Gastroenterol Hepatol 3:987–991

    Article  CAS  PubMed  Google Scholar 

  • Saksirisampant W, Nuchprayoon S, Pradniwat P, Lamchuan D (2010) Boeck and Drbohlav Locke egg serum medium for detection of Blastocystis hominis. Chula Med J 54:527–536

    Google Scholar 

  • Santos HJ, Rivera WL (2009) Kinetic analysis of antibody responses to Blastocystis hominis in sera and intestinal secretions of orally infected mice. Parasitol Res 105:1303–1310

    Article  PubMed  Google Scholar 

  • Schumacher JH, O’Garra A, Shrader B, van Kimmenade A, Bond MW, Mosmann TR, Coffman RL (1988) The characterization of four monoclonal antibodies specific for mouse IL-5 and development of mouse and human IL-5 enzyme-linked immunosorbent. J Immunol 141:1576–1581

    CAS  PubMed  Google Scholar 

  • Shlim DR, Hoge CW, Rajah R, Rabold JG, Echeverria P (1995) Is Blastocystis hominis a cause of diarrhea in travelers? A prospective controlled study in Nepal. Clin Infect Dis 21:97–101

    Article  CAS  PubMed  Google Scholar 

  • Sinigaglia F, D’Ambrosio D, Panina-Bordignon P, Rogge L (1999) Regulation of the IL-12/IL-12R axis: a critical step in T-helper cell differentiation and effector function. Immunol Rev 170:65–72

    Article  CAS  PubMed  Google Scholar 

  • Sohail MR, Fischer PR (2005) Blastocystis hominis and travelers. Travel Med Infect Dis 3(1):33–38

    Article  PubMed  Google Scholar 

  • Stark D, van Hal S, Marriott D, Ellis J, Harkness J (2007) Irritable bowel syndrome: a review on the role of intestinal protozoa and the importance of their detection and diagnosis. Int J Parasitol 37:11–20

    Article  CAS  PubMed  Google Scholar 

  • Stensvold CR, Lewis HC, Hammerum AM, Porsbo LJ, Nielsen SS, Olsen KE, Arendrup MC, Nielsen HV, Molbak K (2009) Blastocystis: unraveling potential risk factors and clinical significance of a common but neglected parasite. Epidemiol Infect 137:1655–1663

    Article  CAS  PubMed  Google Scholar 

  • Sukthana Y (2001) Is Blastocystis hominis a Human Pathogenic Protozoan? J Trop Med Parasitol 24:16–22

    Google Scholar 

  • Tan KS (2004) Blastocystis spp. in human and animals: new using modern methodologies. Vet Parasitol 126:121–144

    Article  PubMed  Google Scholar 

  • Tan KS (2008) New insights on classification, identification and clinical relevance of Blastocystis spp. Clin Microbiol Rev 21:639–665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tan TC, Suresh KG (2006) Predominance of amoeboid forms of Blastocystis hominis in isolates from symptomatic patients. Parasitol Res 98:189–193

    Article  CAS  PubMed  Google Scholar 

  • Yakoob J, Jafri W, Jafri N, Khan R, Islam M, Beg MA, Zaman V (2004) Irritable bowel syndrome in search of etiology: roles of Blastocystis hominis. Am Soc Trop Med Hyg 70:383–385

    Google Scholar 

  • Yakoob J, Jafri W, Beg MA, Abbas Z, Naz S, Islam M, Khan R (2010b) Blastocystis hominis and Dientamoeba fragilis in patients fulfilling irritable bowel syndrome criteria. Parasitol Res 107:679–684

  • Yakoob J, Abbas Z, Beg MA, Naz S, Awan S, Hamid S, Jafri W (2011) In vitro sensitivity of Blastocystis hominis to garlic, ginger, white cumin, and black pepper used in diet. Parasitol Res 9:379–385

    Article  Google Scholar 

  • Yao FR, Qiao JY, Zhao Y, Yang JH, Li XQ (2005) Experimental infection of mice with Blastocystis hominis. Chin J Parasitol Parasit Dis 23:444–448

    Google Scholar 

  • Yoshikawa H, Nagashima M, Morimoto K, Yamanouti Y, Yap EH, Singh M (2003) Freezefracture and cytochemical studies on the in vitro cyst form of reptilian Blastocystis spp. pythoni. J Eukaryot Microbiol 50:70–75

    Article  PubMed  Google Scholar 

  • Zhang HM, Li W, Yan QY, He LJ, Su YP (2006) Impact of Blastocystis hominis infection on ultrastructure of intestinal mucosa in mice. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi 24:187–191

    CAS  PubMed  Google Scholar 

  • Zierdt CH (1991) Blastocystis spp. hominis—past and future. Clin Microbiol Rev 4:61–79

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ekhlas H. Abdel-Hafeez.

Ethics declarations

None.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Figure S1

Photomicrographs of various forms of Blastocystis spp. in axenic culture and mice’s feces (x100). a. The axenic culture shows many forms of Blastocystis spp.; the vacuolar form (red arrow) and the granular form (blue arrow). b. In axenic culture, one of the granular form shows multiplication by budding (blue arrow). c. A direct smear of mice’s feces sample shows different forms of Blastocystis spp.; the vacuolar (red arrow), the granular form (blue arrow) and the cyst form (green arrow) (JPG 164 kb)

Figure S2

A photomicrograph of intestine of the infected immunosuppresed mice is showing that Blastocystis (7- 8μm) was dispersed throughout the lamina propria (blue arrow) with numerous eosinophils (green arrow) (JPG 236 kb)

Figure S3

A photomicrograph of the intestinal crypts of the colon of the mice of non-infected immunosuppressed group is showing normal columnar epitheial lining H&E, x 10 (JPG 218 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abdel-Hafeez, E.H., Ahmad, A.K., Abdelgelil, N.H. et al. Immunopathological assessments of human Blastocystis spp. in experimentally infected immunocompetent and immunosuppresed mice. Parasitol Res 115, 2061–2071 (2016). https://doi.org/10.1007/s00436-016-4951-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-016-4951-3

Keywords

Navigation