| Title: |
Pneumococcal interactions with the host : threats and therapeutic approaches |
| Authors: |
Codemo, Mario |
| Publisher Information: |
Inst för mikrobiologi, tumör- och cellbiologi / Dept of Microbiology, Tumor and Cell Biology |
| Publication Year: |
2018 |
| Collection: |
Karolinska Institutet: Publications |
| Description: |
Streptococcus pneumoniae (the pneumococcus) is a Gram-positive bacterium responsible for substantial morbidity and mortality worldwide. Apart from causing severe pneumonia, septicemia or meningitis, pneumococci are also major contributors to less severe diseases like otitis media and sinusitis. Pneumococcal autolysis was thought to be the main route that S. pneumoniae utilizes in order to deliver its virulence factors. Recently a new mechanism has been proposed, the release of extracellular vesicles (EVs). Presence of adhesins and other virulence factors on EVs leads to cell responses after contact with vesicles. We observed that pneumococcal EVs are indeed a mechanism for the delivery of virulence factors to host cells, and that interactions of vesicles with dendritic cells lead to activation of cells and release of pro-inflammatory cytokines. Since EVs mimic the outside of a bacterium, they can play a role as decoys for the immune system. Tightly linked to this decoy function is the ability of EVs to promote immune evasion through binding of serum components. Indeed, we discovered that pneumococcal EVs are able to bind several components of the human complement system, leading to formation of the membrane attack complex on vesicles. Outer membrane vesicles (OMVs) released from Gram-negative bacteria have been directly used as vaccines in numerous preclinical mouse models. We isolated pneumococcal vesicles and found that they are able to confer serotype-independent protection in mice. Moreover, these vesicles stimulate the production of antibodies directed against pneumococcal antigens. These antibodies are able to increase opsonophagocytosis of pneumococci by mouse macrophages, and are required for protection, as demonstrated by the absence of protection in mice that are not able to produce B lymphocytes. Moreover, in our model the vesicles are able to protect mice against an infection with a pneumococcal strain of serotype 3, to a higher degree than what we observed for the currently available pneumococcal ... |
| Document Type: |
doctoral or postdoctoral thesis |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
I. CODEMO M., MUSCHIOL S., IOVINO F., NANNAPANENI P., PLANT L., WAI S. N., HENRIQUES-NORMARK B. Immunomodulatory Effects of Pneumococcal Extracellular Vesicles on Cellular and Humoral Host Defenses. mBio. 2018 Apr 10, 9(2): e00559-18. ::doi::10.1128/mBio.00559-18 ::pmid::29636428 ::isi::000431279600074; II. CODEMO M., IOVINO F., MUSCHIOL S., NANNAPANENI P., HENRIQUES-NORMARK B. Streptococcus pneumoniae microparticles evoke a heterologous serotypeindependent protection towards invasive pneumococcal disease. [Manuscript]; III. NORMAN M., PATHAK A., CODEMO M., SENDER V., GALLOTTA M., NANNAPANENI P., BOOTSMA H. J., BROWALL S., JONCZYK M., HASTE L., HERMANS P., ANDREW P., HENRIQUES-NORMARK B. Growth and defence strategies affect pneumococcal disease pattern: septicaemia versus pneumonia. [Manuscript]; IV. XIE S., SPELMINK L., CODEMO M., SUBRAMANIAN K., PÜTSEP K., HENRIQUES-NORMARK B., OLLIVER M. Cinobufagin Modulates Human Innate Immune Responses and Triggers Antibacterial Activity. PLoS ONE. 2016 Aug 16; 11(8): e0160734. ::doi::10.1371/journal.pone.0160734 ::pmid::27529866 ::isi::000381476700019; http://hdl.handle.net/10616/46335 |
| Availability: |
http://hdl.handle.net/10616/46335 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.8BDEC6B3 |
| Database: |
BASE |