Mechanisms Causing the Inflammatory Response to Streptococcus pneumoniae

Humans have frequent contact with pneumococcus that commonly results in carriage, occasionally causes disease, and rarely causes death. Mucosal exposure to pneumococcus is managed with a high degree of immunological tolerance, where carriage is chaperoned by regulatory T cells. Alveolar macrophages are sentinels at whose signal the airspaces are aggressively defended, predominantly by neutrophils, and the ensuing debris efficiently managed by a role change among the remaining resident alveolar macrophages. Bloodstream invasion and meningitis cause chaos for host and pathogen, with dysregulated inflammation threatening both; extensive bacterial killing occurs despite pathogen survival strategies, and the host requires substantial support to maintain organ functions. In this chapter, the tissue-specific mechanisms for these compartmentalized responses are discussed in the context of translational research aiming for improved prevention and treatment of pneumococcal disease.