Imperial College London
Alternate

ProfessorCristinaLo Celso

Faculty of Natural Sciences, Department of Life Sciences

Co-Director Centre for Haematology & Prof Stem Cell Biology
 
 
 
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Contact

 

c.lo-celso

 
 
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Location

 

548Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Vainieri:2016:10.1098/rsob.160038,
author = {Vainieri, ML and Blagborough, AM and MacLean, AL and Haltalli, MLR and Ruivo, N and Fletcher, HA and Stumpf, MPH and Sinden, RE and Lo, Celso C},
doi = {10.1098/rsob.160038},
journal = {Open Biology},
title = {Systematic tracking of altered haematopoiesis during sporozoite-mediated malaria development reveals multiple response points},
url = {http://dx.doi.org/10.1098/rsob.160038},
volume = {6},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Haematopoiesis is the complex developmental process that maintainsthe turn-over of all blood cell lineages. It critically depends on the correct functioning of rare, quiescent haematopoietic stem cells (HSCs) and more numerous, HSC-derived, highly proliferative and differentiating haematopoietic progenitor cells (HPCs). Infection is known to affect HSCs, with severe and chronic inflammatory stimuli leading to stem cell pool depletion, while acute, non-lethal infections exert transient and even potentiating effects. Both whetherthis paradigm applies to all infections and whether the HSC response is the dominant driver of the changes observed during stressed haematopoiesis remain open questions. We use a mouse model of malaria, based on natural, sporozoite-driven Plasmodium bergheiinfection as an experimental platform to gain a global view of haematopoietic perturbations during infection progression. We observe coordinated responses by the most primitive HSCs and multiple HPCs, some starting before blood parasitaemia is detected. Weshow that, despite highly variable inter-host responses, primitive HSCsbecome highly proliferative, but mathematical modelling suggests that this alone is not sufficient to significantly impact the whole haematopoietic cascade. We observe that the dramatic expansion of Sca-1þ progenitors results from combined proliferation of direct HSC progeny and phenotypic changes in downstream populations. We observe that the simultaneous perturbation of HSC/HPC population dynamics is coupled with early signs of anaemia onset. Our data uncover a complex relationship between Plasmodium and itshost’s haematopoiesis and raise the question whether the variable responses observed may affect the outcome of the infection itself and its long-term consequences on the host.
AU  - Vainieri,ML
AU  - Blagborough,AM
AU  - MacLean,AL
AU  - Haltalli,MLR
AU  - Ruivo,N
AU  - Fletcher,HA
AU  - Stumpf,MPH
AU  - Sinden,RE
AU  - Lo,Celso C
DO  - 10.1098/rsob.160038
PY  - 2016///
SN  - 2046-2441
TI  - Systematic tracking of altered haematopoiesis during sporozoite-mediated malaria development reveals multiple response points
T2  - Open Biology
UR  - http://dx.doi.org/10.1098/rsob.160038
UR  - http://hdl.handle.net/10044/1/33612
VL  - 6
ER  -
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