• Praziquantel and factor H recr...

*Result*: Praziquantel and factor H recruitment differentially affect the susceptibility of Schistosoma mansoni to complement-mediated damage.

Title:
Praziquantel and factor H recruitment differentially affect the susceptibility of Schistosoma mansoni to complement-mediated damage.
Authors:
van Beek AE; Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Allschwil, Switzerland.; University of Basel, Basel, Switzerland., Jeanguenat H; Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Allschwil, Switzerland.; University of Basel, Basel, Switzerland., Häberli C; Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Allschwil, Switzerland.; University of Basel, Basel, Switzerland., Pouw RB; Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.; Sanquin Research and Landsteiner Laboratory of the Amsterdam University Medical Centers (UMC), University of Amsterdam, Amsterdam, Netherlands., Lamers C; Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland., Pál G; Department of Biochemistry, Eötvös Loránd University, Budapest, Hungary., Gál P; Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Hungarian Research Network, Budapest, Hungary., Schmidt CQ; Institute of Experimental and Clinical Pharmacology, Toxicology and Pharmacology of Natural Products, University of Ulm Medical Center, Ulm, Germany., Ricklin D; Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland., Keiser J; Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Allschwil, Switzerland.; University of Basel, Basel, Switzerland.
Source:
Frontiers in immunology [Front Immunol] 2024 Nov 12; Vol. 15, pp. 1474358. Date of Electronic Publication: 2024 Nov 12 (Print Publication: 2024).
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE
Imprint Name(s):
Original Publication: [Lausanne : Frontiers Research Foundation]
MeSH Terms:
Schistosoma mansoni*/immunology , Complement Factor H*/metabolism , Complement Factor H*/immunology , Praziquantel*/pharmacology, Schistosomiasis mansoni/immunology ; Schistosomiasis mansoni/parasitology ; Complement Activation/drug effects ; Complement System Proteins/immunology ; Complement System Proteins/metabolism ; Host-Parasite Interactions/immunology ; Anthelmintics/pharmacology ; Anthelmintics/therapeutic use ; Animals ; Humans ; Disease Susceptibility ; Mice ; Life Cycle Stages
References:
Exp Parasitol. 1973 Feb;33(1):56-72. (PMID: 4348075)
Amino Acids. 2021 Jan;53(1):143-147. (PMID: 33398524)
Front Immunol. 2018 Jul 12;9:1607. (PMID: 30050540)
Acta Trop. 2000 May 31;75(3):341-8. (PMID: 10838218)
Parasitology. 1992;105 Suppl:S41-8. (PMID: 1308928)
Bull Soc Pathol Exot Filiales. 1985;78(5):643-7. (PMID: 3936631)
Trends Parasitol. 2020 Feb;36(2):182-194. (PMID: 31787521)
Mol Immunol. 1996 Dec;33(17-18):1389-401. (PMID: 9171898)
Exp Parasitol. 1986 Feb;61(1):86-94. (PMID: 3943595)
Exp Parasitol. 1985 Apr;59(2):204-16. (PMID: 2857654)
Parasitology. 2010 Jan;137(1):85-98. (PMID: 19814844)
Semin Immunopathol. 2020 Jun;42(3):355-371. (PMID: 32076812)
PLoS Negl Trop Dis. 2014 Oct 16;8(10):e3234. (PMID: 25329403)
Parasitol Res. 2014 Oct;113(10):3685-96. (PMID: 25030119)
Mol Immunol. 2007 Apr;44(10):2578-86. (PMID: 17267037)
Front Immunol. 2015 May 26;6:257. (PMID: 26074922)
J Immunol. 1979 Oct;123(4):1551-7. (PMID: 113459)
Proc Natl Acad Sci U S A. 2012 Jun 26;109(26):10498-503. (PMID: 22691502)
Biomolecules. 2022 Oct 26;12(11):. (PMID: 36358913)
J Parasitol. 1973 Aug;59(4):741-3. (PMID: 4722597)
Malar J. 2004 Nov 15;3:43. (PMID: 15544703)
Transplant Proc. 1999 Aug;31(5):2168-71. (PMID: 10456004)
Immunol Rev. 2016 Nov;274(1):152-171. (PMID: 27782321)
Med Res Rev. 1983 Apr-Jun;3(2):147-200. (PMID: 6408323)
Blood Adv. 2019 Feb 26;3(4):621-632. (PMID: 30804016)
Front Immunol. 2021 Feb 25;12:602277. (PMID: 33717083)
J Clin Invest. 1992 Nov;90(5):2000-12. (PMID: 1385479)
Proc Natl Acad Sci U S A. 2020 Aug 11;117(32):19299-19309. (PMID: 32737161)
J Immunol. 2008 Aug 15;181(4):2610-9. (PMID: 18684951)
Exp Parasitol. 2000 Aug;95(4):231-9. (PMID: 11038306)
Immunobiology. 2013 Apr;218(4):496-505. (PMID: 22795972)
J Immunol. 2019 Feb 15;202(4):1200-1209. (PMID: 30635392)
Z Parasitenkd. 1980;63(2):113-28. (PMID: 7456640)
Nat Protoc. 2019 Feb;14(2):461-481. (PMID: 30610241)
Front Immunol. 2020 Jun 09;11:1018. (PMID: 32582161)
J Immunol. 1988 Sep 1;141(5):1602-9. (PMID: 2457622)
PLoS Negl Trop Dis. 2019 Jan 28;13(1):e0006590. (PMID: 30689639)
Exp Parasitol. 1982 Apr;53(2):285-98. (PMID: 7060708)
Protein Expr Purif. 2011 Apr;76(2):254-63. (PMID: 21146613)
Front Immunol. 2015 Jun 02;6:262. (PMID: 26082779)
J Immunol. 1979 Feb;122(2):628-37. (PMID: 762435)
Trends Parasitol. 2022 Jan;38(1):67-79. (PMID: 34389214)
Front Immunol. 2021 Feb 04;11:624178. (PMID: 33613562)
J Immunol. 1986 Jan;136(2):710-5. (PMID: 2416822)
Clin Dermatol. 2001 Sep-Oct;19(5):563-72. (PMID: 11604303)
Mol Biochem Parasitol. 2017 Jul;215:40-46. (PMID: 28011341)
Infect Immun. 1986 Jan;51(1):181-6. (PMID: 3940995)
Nat Commun. 2022 Sep 20;13(1):5519. (PMID: 36127336)
J Immunol. 2013 Jun 1;190(11):5712-21. (PMID: 23616575)
Exp Parasitol. 1980 Oct;50(2):278-86. (PMID: 7409076)
Infect Dis Poverty. 2017 Mar 28;6(1):74. (PMID: 28351414)
Mol Immunol. 2019 Oct;114:49-61. (PMID: 31336249)
J Invest Dermatol. 2000 Jan;114(1):78-82. (PMID: 10620119)
Parasit Vectors. 2018 Nov 6;11(1):580. (PMID: 30400935)
Parasitology. 1981 Jun;82(Pt 3):357-74. (PMID: 7243345)
Parasitology. 1982 Oct;85 (Pt 2):315-23. (PMID: 7145473)
J Thorac Cardiovasc Surg. 2001 Jul;122(1):113-22. (PMID: 11436043)
Trends Parasitol. 2003 Feb;19(2):63-6; discussion 66-8. (PMID: 12586470)
J Immunol. 2016 Jan 15;196(2):866-76. (PMID: 26643478)
Front Microbiol. 2019 Mar 20;10:532. (PMID: 30949145)
J Biol Chem. 2012 Jun 8;287(24):20290-300. (PMID: 22511776)
Ann Trop Med Parasitol. 1978 Jun;72(3):293-5. (PMID: 666401)
Contributed Indexing:
Keywords: Schistosoma mansoni; complement; complement evasion; complement factor H; host-pathogen interactions; praziquantel
Substance Nomenclature:
80295-65-4 (Complement Factor H)
6490C9U457 (Praziquantel)
9007-36-7 (Complement System Proteins)
0 (Anthelmintics)
Entry Date(s):
Date Created: 20241127 Date Completed: 20241127 Latest Revision: 20241128
Update Code:
20260130
PubMed Central ID:
PMC11588701
DOI:
10.3389/fimmu.2024.1474358
PMID:
39600706
Database:
MEDLINE

*Further Information*

*Background: Schistosomes are highly efficient evaders of human immunity, as evident by their ability to survive in human blood for years. How they protect themselves against the constant attack by a key element of innate immunity, the complement system, has remained unclear. In this study, new light is shed on the interaction between distinct life-cycle stages of Schistosoma mansoni and the human complement system.
Results: We demonstrate that schistosomula, the young stage assumed immediately after cercaria penetration of the skin, are extremely vulnerable towards complement-mediated killing as only 10-20% survive. The survival rate increases to 70% already within 30 minutes and reaches close to 100% within two hours. Pathway-specific complement inhibitors revealed the alternative pathway of complement activation as the main contributor to killing and damage of the schistosomula. Moreover, the complement regulator factor H is recruited by the schistosomula in this early stage to evade killing. Surviving parasites appear fully viable despite the ongoing complement attack, as demonstrated by the deposition of C3 fragments. However, when exposed to the widely used schistocidal drug praziquantel, the vulnerability of 24 h-old schistosomula towards complement-mediated killing is notably increased; no such effect was observed for mefloquine or oxamniquine. Similar to the younger life-cycle stages, adult worms remain under complement attack. C3 fragments were found all over the outer surface (tegument), deposited mostly on the ridges and not on the tubercles.
Conclusion: The recruitment of factor H merits more detailed studies that pinpoint the molecules involved and elucidate the novel possibilities to intercept the uncovered immune evasion therapeutically. That praziquantel and complement work in synergy is surprising and may in the future result in enhanced understanding of the drug's mechanism of action.
(Copyright © 2024 van Beek, Jeanguenat, Häberli, Pouw, Lamers, Pál, Gál, Schmidt, Ricklin and Keiser.)*

*CS is an inventor of patent applications that describes the use of engineered complement inhibitors for therapeutic applications. He has received honoraria for speaking at symposia as well as research funding from the pharmaceutical industry. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.*