Innate immunity associates with protection from pneumococcal colonisation, but colonisation does not confer capsule-independent protection

The study examined nasopharyngeal colonisation with Streptococcus pneumoniae using a controlled human infection model. Healthy adults were intranasally inoculated with serotype 15B at escalating doses, with maximum colonisation rate reaching 31.4% at 8 x 10 CFU per naris. Colonisation with 15B induced capsular polysaccharide-specific IgG antibody response; however, these humoral immune measures did not predict protection from infection. Prior colonisation with serotype 15B did not reduce acquisition of serotype 6B upon re-challenge. Analysis of nasal microbiopsy samples revealed that resistance to colonisation was associated with elevated MIP-1 and MIP-1β levels, while carriage was associated with enhanced chemokine and IL-6 responses. The results suggest that local innate immunity, rather than circulating antibodies alone, may contribute to colonisation control and that experimental colonisation does not provide protection against heterologous serotypes.