An Alternative Role of C1q in Bacterial Infections: Facilitating Streptococcus pneumoniae Adherence and Invasion of Host Cells.

• Streptococcus pneumoniae (pneumococcus) is a major human pathogen, which evolved numerous successful strategies to colonize the host. In this study, we report a novel mechanism of pneumococcal-host interaction, whereby pneumococci use a host complement protein C1q, primarily involved in the host-defense mechanism, for colonization and subsequent dissemination. Using cell-culture infection assays and confocal microscopy, we observed that pneumococcal surface-bound C1q significantly enhanced pneumococcal adherence to and invasion of host epithelial and endothelial cells. Flow cytometry demonstrated a direct, Ab-independent binding of purified C1q to various clinical isolates of pneumococci. This interaction was seemingly capsule serotype independent and mediated by the bacterial surface-exposed proteins, as pretreatment of pneumococci with pronase E but not sodium periodate significantly reduced C1q binding. Moreover, similar binding was observed using C1 complex as the source of C1q. Furthermore, our data show that C1q bound to the pneumococcal surface through the globular heads and with the host cell-surface receptor(s)/glycosaminoglycans via its N-terminal collagen-like stalk, as the presence of C1q N-terminal fragment and low m.w. heparin but not the C-terminal globular heads blocked C1q-mediated pneumococcal adherence to host cells. Taken together, we demonstrate for the first time, to our knowledge, a unique function of complement protein C1q, as a molecular bridge between pneumococci and the host, which promotes bacterial cellular adherence and invasion. Nevertheless, in some conditions, this mechanism could be also beneficial for the host as it may result in uptake and clearance of the bacteria.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

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