title: Pneumococcal pneumonia suppresses allergy development but preserves respiratory tolerance in mice.
abstract: Colonization with Streptococcus pneumoniae (S. pneumoniae) is associated with an increased risk for recurrent wheeze and asthma. Killed S. pneumoniae showed some potential as an effective immunomodulatory therapy in a murine model of asthma. Murine studies demonstrated protection against allergic asthma by symbiotic bacteria via triggering regulatory T cell response: treatment with killed S. pneumoniae resulted in suppressed levels of allergen-specific Th2 cytokines, while early immunization generated a protective Th1 response. We investigated the impact of lung infection with live S. pneumoniae on both the development and maintenance of allergic airway inflammation and respiratory tolerance in mice. BALB/c mice were infected intratracheally with S. pneumoniae either prior to or after tolerance or allergy were induced, using ovalbumin (OVA) as model allergen. Infection of mice with S. pneumoniae prior to sensitization or after manifestation of allergic airway inflammation suppressed the development of an allergic phenotype as judged by reduced eosinophil counts in bronchoalveolar lavage fluid, decreased IgE serum levels and Th2 cytokines, relative to non-infected allergic control mice. In contrast, infection of mice with S. pneumoniae after manifestation of allergic airway inflammation combined with late mucosal re-challenge did not affect the allergic response. Moreover, induction and maintenance of respiratory tolerance to OVA challenge were not altered in S. pneumoniae-infected mice, demonstrating that mice remained tolerant to the model allergen and were protected from the development of allergic airway inflammation regardless of the time point of infection. Our results suggest that a bacterial infection may decrease the manifestation of an allergic phenotype not only prior to sensitization but also after manifestation of allergic airway inflammation in mice, whereas both, induction and maintenance of respiratory tolerance are not affected by pneumococcal pneumonia. These data may point to a role for undisturbed development and maintenance of mucosal tolerance for the prevention of allergic inflammation also in humans.
authors.affiliation: Hannover Medical School, Department of Pediatrics and Adolescent Medicine, Pediatric Pneumology, Allergology and Neonatology, Hannover, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Hartmann
authors.affiliation: Hannover Medical School, Department of Pediatrics and Adolescent Medicine, Pediatric Pneumology, Allergology and Neonatology, Hannover, Germany.
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Behrendt
authors.affiliation: Hannover Medical School, Department of Experimental Pneumology, Hannover, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Henken
authors.affiliation: Hannover Medical School, Department of Pediatrics and Adolescent Medicine, Pediatric Pneumology, Allergology and Neonatology, Hannover, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Wölbeling
authors.affiliation: Hannover Medical School, Department of Experimental Pneumology, Hannover, Germany.
authors.forename: Ulrich A
authors.initials: UA
authors.lastname: Maus
authors.affiliation: Hannover Medical School, Department of Pediatrics and Adolescent Medicine, Pediatric Pneumology, Allergology and Neonatology, Hannover, Germany. Electronic address: hansen.gesine@mh-hannover.de.
authors.forename: Gesine
authors.initials: G
authors.lastname: Hansen
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006967:Hypersensitivity / Q000150:complications* / Q000276:immunology* / Q000378:metabolism; D007108:Immune Tolerance; D007114:Immunization; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D010641:Phenotype; D011018:Pneumonia, Pneumococcal / Q000150:complications* / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000401:mortality; D020545:Respiratory Mucosa / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D012137:Respiratory System / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: D000485:Allergens; D016207:Cytokines; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D010047:Ovalbumin
keywords: Allergic inflammation; Infection; Murine asthma model; Respiratory tolerance; Streptococcus pneumoniae