Protective Contributions against Invasive Streptococcus pneumoniae Pneumonia of Antibody and Th17-Cell Responses to Nasopharyngeal Colonisation

Abstract

The nasopharyngeal commensal bacteria Streptococcus pneumoniae is also a frequent cause of serious infections. Nasopharyngeal colonisation with S. pneumoniae inhibits subsequent re-colonisation by inducing Th17-cell adaptive responses, whereas vaccination prevents invasive infections by inducing antibodies to S. pneumoniae capsular polysaccharides. In contrast, protection against invasive infection after nasopharyngeal colonisation with mutant S. pneumoniae strains was associated with antibody responses to protein antigens. The role of colonisation-induced Th17-cell responses during subsequent invasive infections is unknown. Using mouse models, we show that previous colonisation with S. pneumoniae protects against subsequent lethal pneumonia mainly by preventing bacteraemia with a more modest effect on local control of infection within the lung. Previous colonisation resulted in CD4-dependent increased levels of Th17-cell cytokines during subsequent infectious challenge. However, mice depleted of CD4 cells prior to challenge remained protected against bacteraemia, whereas no protection was seen in antibody deficient mice and similar protection could be achieved through passive transfer of serum. Serum from colonised mice but not antibody deficient mice promoted phagocytosis of S. pneumoniae, and previously colonised mice were able to rapidly clear S. pneumoniae from the blood after intravenous inoculation. Thus, despite priming for a Th17-cell response during subsequent infection, the protective effects of prior colonisation in this model was not dependent on CD4 cells but on rapid clearance of bacteria from the blood by antibody-mediated phagocytosis. These data suggest that whilst nasopharyngeal colonisation induces a range of immune responses, the effective protective responses depend upon the site of subsequent infection.

Importance of Bacterial Replication and Alveolar Macrophage-Independent Clearance Mechanisms during Early Lung Infection with Streptococcus pneumoniae

“…Macrophage phagocytosis of S. pneumoniae is enhanced by antibody (12). However, in mouse models, antibody to S. pneumoniae acquired by previous nasopharyngeal colonization had little effect on S. pneumoniae clearance from the lung at very early time points (13,14).…”

“…Macrophage phagocytosis of S. pneumoniae is enhanced by antibody (12). However, in mouse models, antibody to S. pneumoniae acquired by previous nasopharyngeal colonization had little effect on S. pneumoniae clearance from the lung at very early time points (13,14).In contrast to the extensive data on the role of AMs, there are few data on the relative importance of non-AM-dependent lung immunity against S. pneumoniae. Both smoking and viral respira- Citation Camberlein E, Cohen JM, José R, Hyams CJ, Callard R, Chimalapati S, Yuste J, Edwards LA, Marshall H, van Rooijen N, Noursadeghi M, Brown JS.…”

The new first-line defense: the potential of nasopharyngeal colonization in vaccine strategies

“…[15][16][17][18][19][20][21] These observations suggest that novel vaccine strategies could harness the immunizing effects of nasopharyngeal colonization to prevent serious infections, and this is the subject addressed in this review with a particular focus on the potential of nasopharyngeal colonization for the prevention of S. pneumoniae and N. meningitidis infections, which are used as case studies that illustrate the benefits and potential drawbacks of this approach.…”

“…15,16,18,19 Importantly, intranasal administration of the 6B strain without successful colonization also augmented local mucosal serological responses, 82 showing that exposure of the nasopharynx to the organism can stimulate an immunological response even if colonization was not detected.…”

“…21 In these challenge studies, colonization resulted in cellular and humoral immune responses to S pneumoniae. Data from mouse colonization models indicate that nasopharyngeal colonization leads to Th17-cell responses 16,18,19 that enhance phagocyte recruitment to the nasopharynx, 18,78 and are critical for both the initial clearance of the colonizing strain and subsequent protection against recolonization. The impact of these phagocytic responses is enhanced by the effects of specific antibody via opsonization and agglutination of S. pneumoniae.…”