Influenza Virus Enhances Bacterial Growth in the Lungs through Weakening Capsule Receptor-Mediated Bacterial Capture by Neutrophils

Abstract

Certain serotypes of encapsulated bacteria are more associated with severe pneumonia than others, but the biological reason behind this association has remained largely unknown. This study has uncovered a causal relationship between capsule serotype and virulence phenotype of Streptococcus pneumoniae, a leading cause of community-acquired pneumonia, in mice using isogenic bacteria. Certain high-virulence (HV) serotypes persist in the lungs and lead to severe pneumonia, whereas the low-virulence (LV) serotypes are effectively cleared. The capsule type-dependent difference in virulence is determined by the capsule-binding receptors, which recognize the capsular polysaccharides of the LV serotypes (but not the HV serotypes) and enable pathogen capture by neutrophils through complement activation. The capsule receptor-driven immunity of lung neutrophils is significantly compromised by pre-infection of influenza virus, which enhances the survival and virulence of the LV S. pneumoniae serotypes, and recurs in the heightened pathogenicity of Haemophilus influenzae. This study not only unravels the long-sought mechanistic mystery of serotype-dependent virulence in bacterial lung infections, but also provides an explanation for the well-known pathogenesis synergism between influenza virus and respiratory bacteria. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=160 SRC="FIGDIR/small/622589v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@1464164org.highwire.dtl.DTLVardef@16f34e5org.highwire.dtl.DTLVardef@1f9ad46org.highwire.dtl.DTLVardef@df104d_HPS_FORMAT_FIGEXP M_FIG C_FIG