Cross-protective mucosal immunity mediated by memory Th17 cells against Streptococcus pneumoniae lung infection.
Pneumonia caused by Streptococcus pneumoniae (Sp) remains a leading cause of serious illness and death worldwide. Immunization with conjugated pneumococcal vaccine has lowered the colonization rate and consequently invasive diseases by inducing serotype-specific antibodies. However, many of the current pneumonia cases result from infection by serotype strains not included in the vaccine. In this study, we asked if cross-protection against lung infection by heterologous strains can be induced, and investigated the underlying immune mechanism. We found that immune mice recovered from a prior infection were protected against heterologous Sp strains in the pneumonia challenge model, as evident by accelerated bacterial clearance, reduced pathology, and apoptosis of lung epithelial cells. Sp infection in the lung induced strong T-helper type 17 (Th17) responses at the lung mucosal site. Transfer of CD4+T cells from immune mice provided heterologous protection against pneumonia, and this protection was abrogated by interleukin-17A (IL-17A) blockade. Transfer of memory CD4+T cells from IL-17A-knockout mice failed to provide protection. These results indicate that memory Th17 cells had a key role in providing protection against pneumonia in a serotype-independent manner and suggest the feasibility of developing a broadly protective vaccine against bacterial pneumonia by targeting mucosal Th17 T cells.
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
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Wang
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
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B
Jiang
Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
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Y
Guo
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
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Li
Department of Pharmacology, Center for Translational Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
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Tian
Joan and Sanford I Weill Department of Medicine, Division of Gastroenterology and Hepatology, Department of Microbiology and Immunology, and The Jill Robert's Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, New York, USA.
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Sonnenberg
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Department of Microbiology, NYU School of Medicine, New York, New York, USA.
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Weiser
Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
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Ni
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.|Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
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Shen
D000818:Animals; D058491:Bacterial Load; D002478:Cells, Cultured; D003429:Cross Reactions; D005260:Female; D006801:Humans; D018928:Immunity, Mucosal; D007156:Immunologic Memory; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022242:Pneumococcal Vaccines / Q000276:immunology*; D011014:Pneumonia / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology* / Q000382:microbiology; D013045:Species Specificity; D013296:Streptococcus pneumoniae / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology* / Q000382:microbiology
D020381:Interleukin-17; D022242:Pneumococcal Vaccines