Skip to main content
SpringerLink
Log in

Contribution of Host Immunity to the Development of Entamoeba histolytica-Induced Liver Abscess

  • Conference paper
  • First Online:
Eukaryome Impact on Human Intestine Homeostasis and Mucosal Immunology

  • 454 Accesses

Abstract

Amebic liver abscess (ALA) is a focal destruction of the liver tissue due to infection with the protozoan parasite Entamoeba histolytica (E. histolytica). So far, it is generally accepted that pathogenicity factors of the parasite contribute to tissue damage. However, epidemiological studies as well as data that evolve from respective murine models suggest a contribution of host factors as well. Independent from the infection rates, men have a higher risk to develop ALA compared to women. The mouse model for ALA exhibits the same sex difference and based on this model, we found that IFNγ provided by Natural Killer T cells confers the female resistance towards ALA. This specific immune response is clearly modulated by androgens. Hence, female mice which were substituted with testosterone develop larger abscesses and are less able to control E. histolytica viability in the liver compared to males. In male mice, on the other side, an enhanced CCL2-dependent recruitment of inflammatory Ly6Chi monocytes via the IL-23/IL-17 immune pathological axis is responsible for tissue destruction during ALA development. Furthermore, TNFα, that exhibits a pivotal role in cytotoxicity, is an effector molecule also responsible for increased liver damage in this case. Interestingly, in human asymptomatically infected with E. histolytica, men exhibit higher CCL2 serum levels compared to women, suggesting a similar mechanism to mice underlying the immune response to the parasite. Indeed, there are a variety of phenotypical similarities within the inflammatory monocyte subsets between humans and mice including sex-dependent differences in the expression of the surface receptor for CCL2 as well as a male bias in the production of specific cytokines involved in the recruitment of innate immune cells. In summary, we assume that the host immune response is considerably involved in liver tissue damage due to the strong reactivity of inflammatory monocytes, which is significantly more distinct in male individuals.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

ALA:

Amebic liver abscess

E. histolytica :

Entamoeba histolytica

IFNγ:

Interferon gamma

TNFα:

Tumor necrosis factor alpha

CCL2:

C-C chemokine ligand 2

Ly6C:

Lymphocyte antigen 6 complex

IL-23:

Interleukin 23

IL-17:

Interleukin 17

αGalCer:

αGalactosylceramide

References

  • Blessmann, J., et al. (2003). Longitudinal study of intestinal Entamoeba histolytica infections in asymptomatic adult carriers. Journal of Clinical Microbiology, 41, 4745–4750.

    PubMed  PubMed Central  Google Scholar 

  • Leippe, M. (1997). Amoebapores. Parasitology Today (Personal ed), 13, 178–183.

    Google Scholar 

  • Bruchhaus, I., Loftus, B. J., Hall, N., & Tannich, E. (2003). The intestinal protozoan parasite Entamoeba histolytica contains 20 cysteine protease genes, of which only a small subset is expressed during in vitro cultivation. Eukaryotic Cell, 2, 501–509.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Matthiesen, J., et al. (2013). Overexpression of specific cysteine peptidases confers pathogenicity to a nonpathogenic Entamoeba histolytica clone. MBio, 4.

    Google Scholar 

  • Stanley, S. L., Jr., Zhang, T., Rubin, D., & Li, E. (1995). Role of the Entamoeba histolytica cysteine proteinase in amebic liver abscess formation in severe combined immunodeficient mice. Infection and Immunity, 63, 1587–1590.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Meyer, M., et al. (2016). Overexpression of differentially expressed genes identified in non-pathogenic and pathogenic Entamoeba histolytica clones allow identification of new pathogenicity factors involved in amoebic liver abscess formation. PLoS Pathogens, 12, e1005853.

    PubMed  PubMed Central  Google Scholar 

  • Acuna-Soto, R., Maguire, J. H., & Wirth, D. F. (2000). Gender distribution in asymptomatic and invasive amebiasis. The American Journal of Gastroenterology, 95, 1277–1283.

    CAS  PubMed  Google Scholar 

  • Kadel, S., & Kovats, S. (2018). Sex hormones regulate innate immune cells and promote sex differences in respiratory virus infection. Frontiers in Immunology, 9, 1653.

    PubMed  PubMed Central  Google Scholar 

  • Klein, S. L. (2004). Hormonal and immunological mechanisms mediating sex differences in parasite infection. Parasite Immunology, 26, 247–264.

    CAS  PubMed  Google Scholar 

  • Markle, J. G., & Fish, E. N. (2014). SeXX matters in immunity. Trends in Immunology, 35, 97–104.

    CAS  PubMed  Google Scholar 

  • Klein, S. L., & Flanagan, K. L. (2016). Sex differences in immune responses. Nature Reviews Immunology, 16, 626–638.

    CAS  PubMed  Google Scholar 

  • Klein, S. L., & Pekosz, A. (2014). Sex-based biology and the rational design of influenza vaccination strategies. The Journal of Infectious Diseases, 209(Suppl 3), S114–S119.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bernin, H., et al. (2014). Immune markers characteristic for asymptomatically infected and diseased Entamoeba histolytica individuals and their relation to sex. BMC Infectious Diseases, 14, 621.

    PubMed  PubMed Central  Google Scholar 

  • Reed, S. L., & Gigli, I. (1990). Lysis of complement-sensitive Entamoeba histolytica by activated terminal complement components. Initiation of complement activation by an extracellular neutral cysteine proteinase. The Journal of Clinical Investigation, 86, 1815–1822.

    Google Scholar 

  • Snow, M., Chen, M., Guo, J., Atkinson, J., & Stanley, S. L., Jr. (2008). Differences in complement-mediated killing of Entamoeba histolytica between men and women—An explanation for the increased susceptibility of men to invasive amebiasis? The American Journal of Tropical Medicine and Hygiene, 78, 922–923.

    PubMed  Google Scholar 

  • Forster, B., Ebert, F., & Horstmann, R. D. (1994). Complement sensitivity of Entamoeba histolytica and various nonpathogenic amoeba species. Tropical Medicine and Parasitology, 45, 355–356.

    CAS  PubMed  Google Scholar 

  • Urban, B., Blasig, C., Forster, B., Hamelmann, C., & Horstmann, R. D. (1996). Putative serine/threonine protein kinase expressed in complement-resistant forms of Entamoeba histolytica. Molecular and Biochemical Parasitology, 80, 171–178.

    CAS  PubMed  Google Scholar 

  • Spiegelberg, H. L. (1989). Biological role of different antibody classes. International Archives of Allergy and Immunology, 90(Suppl. 1), 22–27.

    CAS  Google Scholar 

  • Seguin, R., Mann, B. J., Keller, K., & Chadee, K. (1997). The 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. Infection and Immunity, 65, 2522–2527.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tupin, E., Kinjo, Y., & Kronenberg, M. (2007). The unique role of natural killer T cells in the response to microorganisms. Nature Reviews Microbiology, 5, 405–417.

    CAS  PubMed  Google Scholar 

  • Godfrey, D. I., Stankovic, S., & Baxter, A. G. (2010). Raising the NKT cell family. Nature Immunology, 11, 197–206.

    CAS  PubMed  Google Scholar 

  • Bernin, H., Fehling, H., Marggraff, C., Tannich, E., & Lotter, H. (2016). The cytokine profile of human NKT cells and PBMCs is dependent on donor sex and stimulus. Medical Microbiology and Immunology, 205, 321–332.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sandberg, J. K., Bhardwaj, N., & Nixon, D. F. (2003). Dominant effector memory characteristics, capacity for dynamic adaptive expansion, and sex bias in the innate Valpha24 NKT cell compartment. European Journal of Immunology, 33, 588–596.

    CAS  PubMed  Google Scholar 

  • Lotter, H., et al. (2009). Natural killer T cells activated by a lipopeptidophosphoglycan from Entamoeba histolytica are critically important to control amebic liver abscess. PLoS Pathogens, 5, e1000434.

    PubMed  PubMed Central  Google Scholar 

  • Lotter, H., Jacobs, T., Gaworski, I., & Tannich, E. (2006). Sexual dimorphism in the control of amebic liver abscess in a mouse model of disease. Infection and Immunity, 74, 118–124.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mattner, J., et al. (2005). Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections. Nature, 434, 525–529.

    CAS  PubMed  Google Scholar 

  • Gonzalez-Aseguinolaza, G., et al. (2000). alpha -galactosylceramide-activated Valpha 14 natural killer T cells mediate protection against murine malaria. Proceedings of the National Academy of Sciences of the United States of America, 97, 8461–8466.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Duthie, M. S., & Kahn, S. J. (2002). Treatment with alpha-galactosylceramide before Trypanosoma cruzi infection provides protection or induces failure to thrive. Journal of Immunology (Baltimore, Md: 1950), 168, 5778–5785.

    Google Scholar 

  • Blessmann, J., et al. (2002). Epidemiology of amebiasis in a region of high incidence of amebic liver abscess in central Vietnam. The American Journal of Tropical Medicine and Hygiene, 66, 578–583.

    PubMed  Google Scholar 

  • Gil-Barbosa, M., Fastag de Shor, A., De la Torre, M., & Villegas-Gonzalez, J. (1972). Sequence of amebic hepatic lesions in the rabbit. Archives of Medical Research (Mex), 2(Suppl. 2), 349–354.

    Google Scholar 

  • Roncolato, E. C., Teixeira, J. E., Barbosa, J. E., Zambelli Ramalho, L. N., & Huston, C. D. (2015). Immunization with the Entamoeba histolytica surface metalloprotease EhMSP-1 protects hamsters from amebic liver abscess. Infection and Immunity, 83, 713–720.

    PubMed  PubMed Central  Google Scholar 

  • Chadee, K., & Meerovitch, E. (1984). The pathogenesis of experimentally induced amebic liver abscess in the gerbil (Meriones unguiculatus). The American Journal of Pathology, 117, 71–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Seydel, K. B., Zhang, T., & Stanley, S. L., Jr. (1997). Neutrophils play a critical role in early resistance to amebic liver abscesses in severe combined immunodeficient mice. Infection and Immunity, 65, 3951–3953.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Seydel, K. B., Smith, S. J., & Stanley, S. L., Jr. (2000). Innate immunity to amebic liver abscess is dependent on gamma interferon and nitric oxide in a murine model of disease. Infection and Immunity, 68, 400–402.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lin, J. Y., & Chadee, K. (1992). Macrophage cytotoxicity against Entamoeba histolytica trophozoites is mediated by nitric oxide from L-arginine. Journal of Immunology (Baltimore, Md: 1950), 148, 3999–4005.

    Google Scholar 

  • Velazquez, C., Shibayama-Salas, M., Aguirre-Garcia, J., Tsutsumi, V., & Calderon, J. (1998). Role of neutrophils in innate resistance to Entamoeba histolytica liver infection in mice. Parasite Immunology, 20, 255–262.

    CAS  PubMed  Google Scholar 

  • Jarillo-Luna, R. A., Campos-Rodriguez, R., & Tsutsumi, V. (2000). Participation of neutrophils, macrophages, and endothelial cells in the amebic liver lesion in the mouse. Archives of Medical Research, 31, S101–S103.

    CAS  PubMed  Google Scholar 

  • Lotter, H., et al. (2013). Testosterone increases susceptibility to amebic liver abscess in mice and mediates inhibition of IFNgamma secretion in natural killer T cells. PLoS ONE, 8, e55694.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gourdy, P., et al. (2005). Relevance of sexual dimorphism to regulatory T cells: Estradiol promotes IFN-gamma production by invariant natural killer T cells. Blood, 105, 2415–2420.

    CAS  PubMed  Google Scholar 

  • Subleski, J. J., & Ortaldo, J. R. (2009). Editorial: NKT cells: To suppress or not to suppress, that is the question. Journal of Leukocyte Biology, 86, 751–752.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kenna, T., et al. (2003). NKT cells from normal and tumor-bearing human livers are phenotypically and functionally distinct from murine NKT cells. Journal of Immunology (Baltimore, Md: 1950), 171, 1775–1779.

    Google Scholar 

  • Roberts, C. W., Walker, W., & Alexander, J. (2001). Sex-associated hormones and immunity to protozoan parasites. Clinical Microbiology Reviews, 14, 476–488.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bouman, A., Schipper, M., Heineman, M. J., & Faas, M. M. (2004). Gender difference in the non-specific and specific immune response in humans. American Journal of Reproductive Immunology (New York, NY: 1989), 52, 19–26.

    Google Scholar 

  • Gubbels Bupp, M. R., & Jorgensen, T. N. (2018). Androgen-induced immunosuppression. Frontiers in Immunology, 9, 794.

    PubMed  PubMed Central  Google Scholar 

  • Kissick, H. T., et al. (2014). Androgens alter T-cell immunity by inhibiting T-helper 1 differentiation. Proceedings of the National Academy of Sciences, 111, 9887.

    CAS  Google Scholar 

  • Nathan, C. (2006). Neutrophils and immunity: Challenges and opportunities. Nature Reviews Immunology, 6, 173–182.

    CAS  PubMed  Google Scholar 

  • Laskin, D. L., Sunil, V. R., Gardner, C. R., & Laskin, J. D. (2011). Macrophages and tissue injury: Agents of defense or destruction? Annual Review of Pharmacology and Toxicology, 51, 267–288.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Guilliams, M., et al. (2014). Dendritic cells, monocytes and macrophages: A unified nomenclature based on ontogeny. Nature Reviews Immunology, 14, 571–578.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ziegler-Heitbrock, L., et al. (2010). Nomenclature of monocytes and dendritic cells in blood. Blood, 116, e74–e80.

    CAS  PubMed  Google Scholar 

  • Zimmermann, H., Trautwein, C., & Tacke, F. (2012). Functional role of monocytes and macrophages for the inflammatory response in acute liver injury. Frontiers in Physiology 3.

    Google Scholar 

  • Shi, C., & Pamer, E. G. (2011). Monocyte recruitment during infection and inflammation. Nature Reviews Immunology, 11, 762–774.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Patel, A. A., et al. (2017). The fate and lifespan of human monocyte subsets in steady state and systemic inflammation. The Journal of Experimental Medicine, 214, 1913–1923.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Serbina, N. V., & Pamer, E. G. (2006). Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nature Immunology, 7, 311–317.

    CAS  PubMed  Google Scholar 

  • Helk, E., et al. (2013). TNFalpha-mediated liver destruction by Kupffer cells and Ly6Chi monocytes during Entamoeba histolytica infection. PLoS Pathogens, 9, e1003096.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bouman, A., Heineman, M. J., & Faas, M. M. (2005). Sex hormones and the immune response in humans. Human Reproduction Update, 11, 411–423.

    CAS  PubMed  Google Scholar 

  • Bosschaerts, T., et al. (2010). Tip-DC development during parasitic infection is regulated by IL-10 and requires CCL2/CCR2, IFN-gamma and MyD88 signaling. PLoS Pathogens, 6, e1001045.

    PubMed  PubMed Central  Google Scholar 

  • Terrazas, C., et al. (2017). Ly6C(hi) inflammatory monocytes promote susceptibility to Leishmania donovani infection. Scientific Reports, 7, 14693.

    PubMed  PubMed Central  Google Scholar 

  • Dunlap, M. D., et al. (2018). A novel role for C-C motif chemokine receptor 2 during infection with hypervirulent Mycobacterium tuberculosis. Mucosal Immunology, 11, 1727–1742.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gurczynski, S. J., et al. (2019). CCR2 mediates increased susceptibility to post-H1N1 bacterial pneumonia by limiting dendritic cell induction of IL-17. Mucosal Immunology, 12, 518–530.

    CAS  PubMed  Google Scholar 

  • Geissmann, F., Jung, S., & Littman, D. R. (2003). Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity, 19, 71–82.

    CAS  PubMed  Google Scholar 

  • Uversky, V. N., et al. (2017). Functionality of intrinsic disorder in tumor necrosis factor-alpha and its receptors. FEBS Journal, 284, 3589–3618.

    CAS  PubMed  Google Scholar 

  • Gaffen, S. L., Jain, R., Garg, A. V., & Cua, D. J. (2014). The IL-23-IL-17 immune axis: From mechanisms to therapeutic testing. Nature Reviews Immunology, 14, 585–600.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Paust, H. J., et al. (2009). The IL-23/Th17 axis contributes to renal injury in experimental glomerulonephritis. Journal of the American Society of Nephrology, 20, 969–979.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen, K., et al. (2011). IL-17RA is required for CCL2 expression, macrophage recruitment, and emphysema in response to cigarette smoke. PLoS ONE, 6, e20333.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shahrara, S., Pickens, S. R., Dorfleutner, A., & Pope, R. M. (2009). IL-17 induces monocyte migration in rheumatoid arthritis. Journal of Immunology (Baltimore, Md: 1950), 182, 3884–3891.

    Google Scholar 

  • Yang, X. O., et al. (2008). Regulation of inflammatory responses by IL-17F. The Journal of Experimental Medicine, 205, 1063–1075.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Noll, J., et al. (2016). IL-23 prevents IL-13-dependent tissue repair associated with Ly6C(lo) monocytes in Entamoeba histolytica-induced liver damage. Journal of Hepatology, 64, 1147–1157.

    CAS  PubMed  Google Scholar 

  • Dal-Secco, D., et al. (2015). A dynamic spectrum of monocytes arising from the in situ reprogramming of CCR2+ monocytes at a site of sterile injury. The Journal of Experimental Medicine, 212, 447–456.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the German Research Foundation within Collaborative Research Centre 841 and by the State Research Funding Hamburg, LFF-FV45, Hamburg, Germany.

Author information

Authors and Affiliations

  1. Department of Molecular Parasitology, Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Str. 74, 20359, Hamburg, Germany

    Julie Sellau & Hanna Lotter

Authors
  1. Julie Sellau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hanna Lotter
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hanna Lotter .

Editor information

Editors and Affiliations

  1. Institute Pasteur, Paris, France

    Nancy Guillen

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this paper

Check for updates. Verify currency and authenticity via CrossMark

Cite this paper

Sellau, J., Lotter, H. (2020). Contribution of Host Immunity to the Development of Entamoeba histolytica-Induced Liver Abscess. In: Guillen, N. (eds) Eukaryome Impact on Human Intestine Homeostasis and Mucosal Immunology. Springer, Cham. https://doi.org/10.1007/978-3-030-44826-4_11

Download citation

Publish with us

Policies and ethics

Search

Navigation