title: Protection against Streptococcus pneumoniae lung infection after nasopharyngeal colonization requires both humoral and cellular immune responses.
abstract: Streptococcus pneumoniae is a common cause of pneumonia and infective exacerbations of chronic lung disease, yet there are few data on how adaptive immunity can specifically prevent S. pneumoniae lung infection. We have used a murine model of nasopharyngeal colonization by the serotype 19F S. pneumoniae strain EF3030 followed by lung infection to investigate whether colonization protects against subsequent lung infection and the mechanisms involved. EF3030 colonization induced systemic and local immunoglobulin G against a limited number of S. pneumoniae protein antigens rather than capsular polysaccharide. During lung infection, previously colonized mice had increased early cytokine responses and neutrophil recruitment and reduced bacterial colony-forming units in the lungs and bronchoalveolar lavage fluid compared with control mice. Colonization-induced protection was lost when experiments were repeated in B-cell- or neutrophil-deficient mice. Furthermore, the improved interleukin (IL)-17 response to infection in previously colonized mice was abolished by depletion of CD4+ cells, and prior colonization did not protect against lung infection in mice depleted of CD4+ cells or IL17. Together these data show that naturally acquired protective immunity to S. pneumoniae lung infection requires both humoral and cell-mediated immune responses, providing a template for the design of improved vaccines that can specifically prevent pneumonia or acute bronchitis.
authors.affiliation: Centre for Inflammation and Tissue Repair, Division of Medicine, University College Medical School, Rayne Institute, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Wilson
authors.affiliation: Infectious Diseases and Microbiology Unit, UCL Institute of Child Health, London, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Cohen
authors.affiliation: Centre for Inflammation and Tissue Repair, Division of Medicine, University College Medical School, Rayne Institute, London, UK.
authors.forename: R J
authors.initials: RJ
authors.lastname: Jose
authors.affiliation: Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: de Vogel
authors.affiliation: Clinical Immunology Department, Papworth Hospital NHS Foundation Trust, Cambridge, UK.
authors.forename: H
authors.initials: H
authors.lastname: Baxendale
authors.affiliation: Centre for Inflammation and Tissue Repair, Division of Medicine, University College Medical School, Rayne Institute, London, UK.
authors.forename: J S
authors.initials: JS
authors.lastname: Brown
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D000942:Antigens, Bacterial / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000382:microbiology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology / Q000382:microbiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D015169:Colony Count, Microbial; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000096:biosynthesis*; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology*; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D009305:Nasopharynx / Q000276:immunology / Q000382:microbiology; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D011135:Polysaccharides, Bacterial / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007074:Immunoglobulin G; D020381:Interleukin-17; D011135:Polysaccharides, Bacterial