Mouse dendritic cells pulsed with capsular polysaccharide induce resistance to lethal pneumococcal challenge: roles of T cells and B cells.
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.
Department of Immunology, the Weizmann Institute of Science, Rehovot, Israel.
Noam
N
Cohen
Raanan
R
Margalit
Meirav
M
Pevsner-Fischer
Simon
S
Yona
Steffen
S
Jung
Lea
L
Eisenbach
Irun R
IR
Cohen
D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology; D055610:Antigens, CD1d / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D010537:Peritoneum / Q000276:immunology / Q000382:microbiology; D011008:Pneumococcal Infections / Q000276:immunology* / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000172:deficiency / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D055610:Antigens, CD1d; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma