Importance of bacterial replication and alveolar macrophage-independent clearance mechanisms during early lung infection with Streptococcus pneumoniae.

Infect Immun. 2015 Jan 12. pii: IAI.02788-14. [Epub ahead of print]

Importance of bacterial replication and alveolar macrophage-independent clearance mechanisms during early lung infection with Streptococcus pneumoniae.

Camberlein E1, Cohen JM2, José R1, Hyams CJ1, Callard R3, Chimalapati S1, Yuste J4, Edwards LA1, Marshall H1, van Rooijen N5, Noursadeghi M6, Brown JS7.

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Abstract

Although the importance of alveolar macrophages for host immunity during early Streptococcus pneumoniae lung infection is well established, the contribution and relative importance of other innate immunity mechanisms and of bacterial factors is less clear. We have used a murine model of S. pneumoniae early lung infection with wild-type, unencapsulated and para-amino benzoic acid auxotroph mutant TIGR4 strains to assess the effects of inoculum size, bacterial replication, the capsule, and alveolar macrophage-dependent and -independent clearance mechanisms on bacterial persistence within the lungs. Alveolar macrophage-dependent and -independent (calculated indirectly) clearance half-lives and bacterial replication doubling times were estimated using a mathematical model. In this model after infection with a high dose inoculum of encapsulated S. pneumoniae alveolar macrophage-independent clearance mechanisms were dominant, with a clearance half-life of 24 minutes compared to 135 minutes for alveolar macrophage-dependent clearance. In addition, after a high dose inoculum successful lung infection required rapid bacterial replication, with an estimated S. pneumoniae doubling time of 16 minutes. The capsule had wide effects on early lung clearance mechanisms, with reduced half-lives of 14 minutes for alveolar-independent and 31 minutes for alveolar macrophage-dependent clearance of unencapsulated bacteria. In contrast, with a lower dose inoculum, the bacterial doubling time increased to 56 minutes and the S. pneumoniae alveolar macrophage-dependent clearance half-life improved to 42 minutes and was largely unaffected by the capsule. These data demonstrate the large effects of bacterial factors (inoculum size, the capsule, rapid replication) and alveolar macrophage-independent clearance mechanisms during early lung infection with S. pneumoniae.

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PMID: 25583525 [PubMed - as supplied by publisher]