Antibody-independent, interleukin-17A-mediated, cross-serotype immunity to pneumococci in mice immunized intranasally with the cell wall polysaccharide.
Serotype-specific immunity to Streptococcus pneumoniae is conferred by antibodies to the capsular polysaccharides, which define the 90 known serotypes. Whether antibody to the species-common cell wall polysaccharide (C-Ps) is protective has been a matter of controversy. Here we show that C-Ps given intranasally with mucosal adjuvant increased the resistance of mice to experimental nasopharyngeal colonization by capsulated S. pneumoniae of serotype 6B. This immunity could be induced in mice congenitally lacking immunoglobulin but was dependent upon CD4+ T cells. Elimination of the charged amino group on the polymer backbone by N acetylation of C-Ps reduced the immunity, as did treatment of the mice with antibody to the cytokine interleukin-17A at the time of challenge, both consistent with the hypothesis of T-cell activation due to the zwitterionic motif of the polymer. C-Ps also protected in a model of fatal aspiration pneumonia by heavily capsulated serotype 3. These findings suggest a novel immunization strategy against S. pneumoniae.
Division of Infectious Diseases, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA. Richard.Malley@childrens.harvard.edu
Richard
R
Malley
Amit
A
Srivastava
Marc
M
Lipsitch
Claudette M
CM
Thompson
Claire
C
Watkins
Arthur
A
Tzianabos
Porter W
PW
Anderson
D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000502:physiology*; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002473:Cell Wall / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D020381:Interleukin-17 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D009302:Nasopharyngeal Diseases / Q000276:immunology / Q000517:prevention & control; D011008:Pneumococcal Infections / Q000276:immunology / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D011018:Pneumonia, Pneumococcal / Q000276:immunology / Q000517:prevention & control; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D021122:Protein Subunits / Q000502:physiology; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification* / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007074:Immunoglobulin G; D020381:Interleukin-17; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; D021122:Protein Subunits