Back to Search
Start Over
The Trypanosoma Brucei KIFC1 Kinesin Ensures the Fast Antibody Clearance Required for Parasite Infectivity
- Source :
- iScience, 23 (9, iScience, iScience, Elsevier, 2020, 23 (9), pp.101476. ⟨10.1016/j.isci.2020.101476⟩, iScience, Vol. 23, no.9, p. 101476 (2020), iScience, Vol 23, Iss 9, Pp 101476-(2020)
- Publication Year :
- 2020
-
Abstract
- Summary Human innate immunity to Trypanosoma brucei involves the trypanosome C-terminal kinesin TbKIFC1, which transports internalized trypanolytic factor apolipoprotein L1 (APOL1) within the parasite. We show that TbKIFC1 preferentially associates with cholesterol-containing membranes and is indispensable for mammalian infectivity. Knockdown of TbKIFC1 did not affect trypanosome growth in vitro but rendered the parasites unable to infect mice unless antibody synthesis was compromised. Surface clearance of Variant Surface Glycoprotein (VSG)-antibody complexes was far slower in these cells, which were more susceptible to capture by macrophages. This phenotype was not due to defects in VSG expression or trafficking but to decreased VSG mobility in a less fluid, stiffer surface membrane. This change can be attributed to increased cholesterol level in the surface membrane in TbKIFC1 knockdown cells. Clearance of surface-bound antibodies by T. brucei is therefore essential for infectivity and depends on high membrane fluidity maintained by the cholesterol-trafficking activity of TbKIFC1.<br />Graphical Abstract<br />Highlights • The TbKIFC1 kinesin preferentially transports cholesterol-containing membranes • TbKIFC1 is absolutely required for parasite growth in mice • Cholesterol trafficking by TbKIFC1 confers high fluidity to the plasma membrane • High membrane fluidity allows antibody clearance necessary for parasite infectivity<br />Immunology; Microbiology Parasite; Cell Biology
- Subjects :
- 0301 basic medicine
Immunology
[SDV.CAN]Life Sciences [q-bio]/Cancer
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
02 engineering and technology
Microbiology Parasite
Trypanosoma brucei
Article
03 medical and health sciences
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
parasitic diseases
Membrane fluidity
[SDV.BV]Life Sciences [q-bio]/Vegetal Biology
[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
lcsh:Science
ComputingMilieux_MISCELLANEOUS
chemistry.chemical_classification
Infectivity
Gene knockdown
Multidisciplinary
Innate immune system
biology
Chemistry
Généralités
Cell Biology
021001 nanoscience & nanotechnology
biology.organism_classification
[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM]
3. Good health
Cell biology
030104 developmental biology
biology.protein
Kinesin
lcsh:Q
Antibody
0210 nano-technology
Glycoprotein
Subjects
Details
- Language :
- English
- ISSN :
- 25890042
- Database :
- OpenAIRE
- Journal :
- iScience, 23 (9, iScience, iScience, Elsevier, 2020, 23 (9), pp.101476. ⟨10.1016/j.isci.2020.101476⟩, iScience, Vol. 23, no.9, p. 101476 (2020), iScience, Vol 23, Iss 9, Pp 101476-(2020)
- Accession number :
- edsair.doi.dedup.....7bb2563011e6db343e3ef31b674ebcb7