Studies on the relation between antigen presentation and mycobacterial trafficking and on the importance of coronin 1 in mycobacterial pathogenesis, neutrophil- and B lymphocyte functions

Combaluzier, Benoit Martial. Studies on the relation between antigen presentation and mycobacterial trafficking and on the importance of coronin 1 in mycobacterial pathogenesis, neutrophil- and B lymphocyte functions. 2008, Doctoral Thesis, University of Basel, Faculty of Science.


Official URL: http://edoc.unibas.ch/diss/DissB_8468

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The immune system developed to prevent infections with pathogenic intruders without inducing
uncontrolled reactions that could be harmful to the host. As a result, the activation of the immune
system is a well-controlled process including recognition of the invading bacteria and cooperation
between different cell types. However, some pathogens can still avoid this immune surveillance by
using multiple and sophisticated mechanisms. A particular notorious example is Mycobacterium
tuberculosis. About one third of the global population has been exposed to this pathogen and while
a healthy person can deal with this infection it can lead to severe symptoms in
immunocompromised patients.
Pathogenic mycobacteria are recognized and internalized inside macrophages where they can block
the maturation of their phagosomes into lysosomes thereby residing and surviving inside host cells.
Firstly, we showed that mycobacteria lacking the virulence factor PknG, an eukaryotic-like
serine/threonine protein kinase, could not resist to lysosomal delivery inside professional antigen
presenting cells. It was then demonstrated that this efficient transfer of the mycobacterium to the
lysosomes did not modify the presentation of mycobacterial peptides on MHC molecules when
compared to wild type mycobacteria residing inside phagosomes. This suggests that the trafficking
of mycobacteria to different organelles does not influence the quality of the antigen presentation.
Coronin 1 is a leukocyte-specific protein that is recruited and retained around phagosomes
containing pathogenic mycobacteria. In the second part of this thesis, we demonstrate that
mycobacteria cannot resist lysosomal delivery when infecting macrophages lacking coronin 1
expression. However, this dramatic change in trafficking is not due to an altered signaling upon
TLRs triggering but to the calcineurin activity that is affected in the absence of coronin 1.
Thirdly we showed that the absence of coronin 1 did not affect the main functions of neutrophils.
The morphology of the neutrophils lacking coronin 1 was not affected as well as several actindependent
processes such as adhesion, spreading, phagocytosis and chemotaxis. The oxidative
burst was also not disturbed in the absence of coronin 1.
Fourthly, this thesis describes the capacity of the immune system to respond against antigens in
mice lacking coronin 1. The absence of coronin 1 did not compromise the ability of the animals to
mount an immune response even if coronin 1 was essential for calcium release in B lymphocytes
upon BCR triggering. These results argue for a general role of coronin 1 in mediating cytosolic
Ca2+ mobilization rather than regulating actin-dependent processes.
Taken together, the results presented in this thesis provide indications for a better understanding of
mycobacteria-host interactions and coronin 1 functions in leukocytes.
Advisors:Pieters, Jean
Committee Members:Finke, Daniela
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Biochemistry (Pieters)
UniBasel Contributors:Pieters, Jean and Finke, Daniela
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:8468
Thesis status:Complete
Number of Pages:152
Identification Number:
edoc DOI:
Last Modified:22 Jan 2018 15:50
Deposited On:03 Jun 2009 12:15

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