gms | German Medical Science

Infektiologie Update 2018: 26. Jahrestagung der Paul-Ehrlich-Gesellschaft für Chemotherapie (PEG)

Paul-Ehrlich-Gesellschaft für Chemotherapie (PEG)

04. - 06.10.2018, Wien, Österreich

Host defense versus immunosuppression: Male and female Schistosoma mansoni differentially impact the host’s immune system

Meeting Abstract

  • Martina Sombetzki - Department of Tropical Medicine and Infectious Diseases, Center of Internal Medicine II, University Medical Center Rostock, Germany
  • Nicole Koslowski - Department of Tropical Medicine and Infectious Diseases, Center of Internal Medicine II, University Medical Center Rostock, Germany
  • Anne Rabes - Department of Tropical Medicine and Infectious Diseases, Center of Internal Medicine II, University Medical Center Rostock, Germany
  • Sonja Seneberg - Department of Tropical Medicine and Infectious Diseases, Center of Internal Medicine II, University Medical Center Rostock, Germany
  • Franziska Winkelmann - Department of Tropical Medicine and Infectious Diseases, Center of Internal Medicine II, University Medical Center Rostock, Germany
  • Carlos Fritzsche - Department of Tropical Medicine and Infectious Diseases, Center of Internal Medicine II, University Medical Center Rostock, Germany
  • Micha Loebermann - Department of Tropical Medicine and Infectious Diseases, Center of Internal Medicine II, University Medical Center Rostock, Germany
  • Emil C. Reisinger - Department of Tropical Medicine and Infectious Diseases, Center of Internal Medicine II, University Medical Center Rostock, Germany

Infektiologie Update 2018. 26. Jahrestagung der Paul-Ehrlich-Gesellschaft für Chemotherapie (PEG). Wien, 04.-06.10.2018. Düsseldorf: German Medical Science GMS Publishing House; 2018. Doc18peg31

doi: 10.3205/18peg31, urn:nbn:de:0183-18peg317

Veröffentlicht: 8. Oktober 2018

© 2018 Sombetzki et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Schistosomiasis remains a major cause of morbidity and mortality, and in the tropics and subtropics, in particular, infection rates are high [1]. The efficacy of anthelmintic therapy is limited since it has no effect on immature parasite stages and does not prevent re-infection. The root cause of the disease is a granulomatous hypersensitivity reaction to parasite eggs entrapped within the intestinal wall and small liver sinusoids. This reaction is mainly caused by CD4+ T cells of the subtype 2 (TH2) and alternatively activated macrophages, which initiate tissue repair but also hepatic fibrosis leading to portal hypertension and its clinical sequelae, ascites and esophageal varices [2].

There are two basic options to reduce egg-induced pathology during Schistosoma spp. infection:

1.
achieving resistance to reinfection, or
2.
dampening down granulomatous hyperreactivity [3].

Mice that were primarily infected with female schistosomes prior to a secondary infection with cercariae of both sexes display a diminished TH2 immune response resulting in reduced granuloma size, hepatic fibrosis, and disease progression [4]. This protection is mediated by the upregulation of CTLA4 which is known to suppress T cell responses. In addition, primary infection with female schistosomes suppresses early innate immune responses against invading cercariae in the skin. In contrast, primary infection with male schistosomes triggers strong innate immune reactions in the skin, resulting in a reduction of worm and egg burden in the liver [5].

We, therefore, propose that the female worm is a neglected player in the dampening down of the host’s immune defense mechanisms and is a promising target for new immune modulatory strategies.


References

1.
Weerakoon KG, Gobert GN, Cai P, McManus DP. Advances in the Diagnosis of Human Schistosomiasis. Clin Microbiol Rev. 2015;28:939-67. DOI: 10.1128/CMR.00137-14 Externer Link
2.
Barron L, Wynn TA. Macrophage activation governs schistosomiasis-induced inflammation and fibrosis. Eur J Immunol. 2011;41(9):2509-14. DOI: 10.1002/eji.201141869. Externer Link
3.
Colley DG, Bustinduy AL, Secor WE, King CH. Human schistosomiasis. The Lancet. 2014;383(9936):2253-64. DOI: 10.1016/S0140-6736(13)61949-2. Externer Link
4.
Koslowski N, Sombetzki M, Loebermann M, Engelmann R, Grabow N, Sterreicher CH, Trauner M, Mueller-Hilke B, Reisinger EC. Single-sex infection with female Schistosoma mansoni cercariae mitigates hepatic fibrosis after secondary infection. PLoS Negl Trop Dis. 2017;11(5):e0005595. DOI: 10.1371/journal.pntd.0005595 Externer Link
5.
Sombetzki M, Koslowski N, Rabes A, Seneberg S, Winkelmann F, Fritzsche C, Loebermann M, Reisinger EC. Host Defense Versus Immunosuppression: Unisexual Infection With Male or Female Schistosoma mansoni Differentially Impacts the Immune Response Against Invading Cercariae. Front Immunol. 2018 Apr 24;9:861. DOI: 10.3389/fimmu.2018.00861.  Externer Link