Cohen, N;
Margalit, R;
Pevsner-Fischer, M;
Yona, S;
Jung, S;
Eisenbach, L;
Cohen, IR;
(2012)
Mouse dendritic cells pulsed with capsular polysaccharide induce resistance to lethal pneumococcal challenge: roles of T cells and B cells.
PLoS One
, 7
(6)
, Article e39193. 10.1371/journal.pone.0039193.
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Abstract
Mice are exceedingly sensitive to intra-peritoneal (IP) challenge with some virulent pneumococci (LD50 = 1 bacterium). To investigate how peripheral contact with bacterial capsular polysaccharide (PS) antigen can induce resistance, we pulsed bone marrow dendritic cells (BMDC) of C57BL/6 mice with type 4 or type 3 PS, injected the BMDC intra-foot pad (IFP) and challenged the mice IP with supra-lethal doses of pneumococci. We examined the responses of T cells and B cells in the draining popliteal lymph node and measured the effects on the bacteria in the peritoneum and blood. We now report that: 1) The PS co-localized with MHC molecules on the BMDC surface; 2) PS-specific T and B cell proliferation and IFNγ secretion was detected in the draining popliteal lymph nodes on day 4; 3) Type-specific resistance to lethal IP challenge was manifested only after day 5; 4) Type-specific IgM and IgG antibodies were detected in the sera of only some of the mice, but B cells were essential for resistance; 5) Control mice vaccinated with a single injection of soluble PS did not develop a response in the draining popliteal lymph node and were not protected; 6) Mice injected with unpulsed BMDC also did not resist challenge: In unprotected mice, pneumococci entered the blood shortly after IP inoculation and multiplied exponentially in both blood and peritoneum killing the mice within 20 hours. Mice vaccinated with PS-pulsed BMDC trapped the bacteria in the peritoneum. The trapped bacteria proliferated exponentially IP, but died suddenly at 18-20 hours. Thus, a single injection of PS antigen associated with intact BMDC is a more effective vaccine than the soluble PS alone. This model system provides a platform for studying novel aspects of PS-targeted vaccination.
| Type: | Article |
|---|---|
| Title: | Mouse dendritic cells pulsed with capsular polysaccharide induce resistance to lethal pneumococcal challenge: roles of T cells and B cells. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0039193 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0039193 |
| Language: | English |
| Additional information: | © 2012 Cohen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC3377650 The financial support for this study was obtained from the Center for the Study of Emerging Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| Keywords: | Animals, Antibody Specificity, Antigen Presentation, Antigens, CD1d, B-Lymphocytes, Dendritic Cells, Female, Histocompatibility Antigens Class I, Histocompatibility Antigens Class II, Immunoglobulin G, Immunoglobulin M, Interferon-gamma, Lymph Nodes, Lymphocyte Activation, Mice, Mice, 129 Strain, Mice, Inbred C57BL, Peritoneum, Pneumococcal Infections, Pneumococcal Vaccines, Polysaccharides, Bacterial, Receptors, Antigen, T-Cell, Streptococcus pneumoniae, T-Lymphocytes, Time Factors |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1349942 |
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