Encyclopedia of Medical Immunology

Living Edition
| Editors: Ian MacKay, Noel R. Rose

APOL-1 Variants, Susceptibility and Resistance to Trypanosomiasis

  • Luis Murguia-Favela
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-9209-2_64-1

Synonyms

Definition

African trypanosomes are flagellate protozoans that are transmitted to mammals after inoculation by flies of the genus Glossina, also known as tsetse flies. Chronic infection with these parasites is fatal if untreated. In humans, the disease is also called “sleeping sickness” and affects thousands of people per year in sub-Saharan Africa (Pays et al. 2014).

Apolipoprotein L1 (APOL-1), an ionic channel-forming protein, is the lytic component of the innate immune system that protects humans against infection from the majority of the African trypanosomes, except for Trypanosoma brucei rhodesiense in East Africa and Trypanosoma brucei gambiense in West Africa. These two species have evolved mechanisms to become resistant to lysis mediated by APOL-1 (Cooper et al. 2016).

In recent years, variants of APOL-1 have been identified that...

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References

  1. Bucheton B, MacLeod A, Jamonneau V. Human host determinants influencing the outcome of Trypanosoma brucei gambiense infections. Parasite Immunol. 2011;33:438–47.CrossRefGoogle Scholar
  2. Cooper A, Capewell P, Clucas C, Veitch N, Weir W, Thomson R, Raper J, MacLeod A. A primate APOL1 variant that kills Trypanosoma brucei gambiense. PLoS Negl Trop Dis. 2016;10(8):1–20.CrossRefGoogle Scholar
  3. Cuypers B, Lecordier L, Meehan CJ, Van den Broeck F, Imamura H, Büscher P, Dujardin JC, Laukens K, Schnaufer A, Dewar C, Lewis M, Balmer O, Azurago T, Kyei-Faried S, Ohene SA, Duah B, Homiah P, Mensah EK, Anleah F, Franco JR, Pays E, Deborggraeve S. Apolipoprotein L1 variant associated with increased susceptibility to trypanosome infection. MBio. 2016;7(2):e02198–15.CrossRefGoogle Scholar
  4. Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI, Bowden DW, Langefeld CD, Oleksyk TK, Uscinski Knob AL, Bernhardy AJ, Hicks PJ, Nelson GW, Vanhollebeke B, Winkler CA, Kopp JB, Pays E, Pollak MR. Association of trypanolitic APOL1 variants with kidney disease in African Americans. Science. 2010;329:841–5.CrossRefGoogle Scholar
  5. Hall JP, Wang H, Barry JD. Mosaic VSGs and the scale of Trypanosoma brucei antigenic variation. PLoS Pathog. 2013;9:e1003502.CrossRefGoogle Scholar
  6. Kieft R, Capewell P, Turner CMR, Veitch NJ, MacLeod A, Hadjuk S. Mechanism of Trypanosoma brucei gambiense (group 1) resistance to human trypanosome lytic factor. PNAS. 2010;107(37):16137–41.CrossRefGoogle Scholar
  7. Limou S, Dummer P, Nelson GW, Kopp JB, Winkler CA. APOL1 toxin, innate immunity and kidney injury. Kidney Int. 2015;88(1):28–34.CrossRefGoogle Scholar
  8. Pays E, Vanhollebeke B, Uzureau P, Lecodier L, Pérez-Morga D. The molecular arms race between African trypanosomiasis and humans. Nat Rev Microbiol. 2014;12:575–84.CrossRefGoogle Scholar
  9. Pérez-Morga D, Vanhollebeke B, Paturiaux-Hanocq F, Nolan DP, Lins L, Homblé F, Vanhamme L, Tebabi P, Pays A, Poelvoorde P, Jacquet A, Brasseur R, Pays E. Apolipoprotein L-1 promotes trypanosome lysis by forming pores in lysosomal membranes. Science. 2005;309:469–72.CrossRefGoogle Scholar
  10. Salmon D. Adenylate cyclases of Trypanosoma brucei inhibit the innate immune response of the host. Science. 2012;337:463–6.CrossRefGoogle Scholar
  11. Samanovic M, Molina-Portela MP, Chessler AD, Burleigh BA, Raper J. Trypanosome lytic factor, an antimicrobial high-density lipoprotein, ameliorates Leishmania infection. PLoS Pathog. 2009;5(1):e1000276.CrossRefGoogle Scholar
  12. Taylor HE, Khatua AK, Popik W. The innate immune factor apolipoprotein L1 restricts HIV-1 infection. J Virol. 2014;88(1):592–603.CrossRefGoogle Scholar
  13. Uzureau P, Uzureau S, Lecordier L, Fontaine F, Tebabi P, Homblé F, Grélard A, Zhendre V, Nolan DP, Lins L, Crowet JM, Pays A, Felu C, Poelvoorde P, Vanhollebeke B, Moestrup SK, Lyngsø J, Pedersen JS, Mottram JC, Dufourc EJ, Pérez-Morga D, Pays E. Mechanism of Trypanosoma brucei gambiense resistance to human serum. Nature. 2013;501:430–4.CrossRefGoogle Scholar
  14. Vanhamme L, Paturiaux-Hanocq F, Poelvoorde P, Nolan DP, Laurence L, Van Den Abbeele J, Pays A, Tebabi P, Van Xong H, Jacquet A, Moguilevsky N, Dieu M, Kane JP, De Baetselier P, Brasseur R, Pays E. Apolipoprotein L-1 is the trypanosome lytic factor of human serum. Nature. 2003;422:83–7.CrossRefGoogle Scholar
  15. Vanhollebeke B, Pays E. The function of apolipoproteins L. Cell Mol Life Sci. 2006;63(17):1937–44.CrossRefGoogle Scholar
  16. Vanhollebeke B, De Muylder G, Nielsen MJ, Pays A, Tebabi P, Dieu M, Raes M, Moestrup SK, Pays E. A haptoglobin-hemoglobin receptor conveys innate immunity to Trypanosoma brucei in humans. Science. 2008;320:677–81.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  1. 1.Alberta Children’s Hospital and The University of CalgaryCalgaryCanada

Section editors and affiliations

  • Stuart Turvey
    • 1
  1. 1.Child & Family Research InstituteVancouverCanada