Pneumococcal pathogenesis: "innate invasion" yet organ-specific damage

Abstract

Streptococcus pneumoniae encounters a variety of unique cellular situations during colonization of the nasopharynx or invasion into the lungs, the bloodstream, or the central nervous system. The ligand/receptor pairings that enable this progression of disease appear to be shared by many respiratory pathogens suggesting that a primitive "innate invasion" mechanism may underlie the well-known species-specific mechanisms of pathogenesis. That the acute phase of the innate immune response includes elements to interrupt this path supports this concept. However, it also appears that each cell type or organ responds differently to activation of this innate invasion pathway leaving some organs, such as the lung, intact post-infection but others, such as the brain, largely destroyed. This review posits a concept of innate invasion but cautions that organ-specific responses complicate opportunities for a simple approach to protect from organ damage.

Fig. 1

Innate invasion versus innate immunity. Schematic representation of pneumococcal cell wall (green with blue teichoic acid) containing PCho (blue circles on teichoic acids) interacting with PAFr (yellow waves) on eukaryotic cells (tan). This innate invasion interaction is counteracted by innate immune defenses such as C reactive protein (orange arcs) and high PCho-containing surfactant (blue ovals)

Fig. 2

Organ-specific cell signaling engendered by PCho cell wall binding to PAFr. PAFr can mediate signaling with or without G protein activation. Epithelial cells are distinguished by G protein activation, no cell wall uptake, activation of ERK, and survival of the cell. Cardiomyocytes, neurons, and endothelial cells take up cell wall without G protein activation. Absence of ERK activation in heart and neuron is associated with cell death

Fig. 3

Schematic model of interaction of PCho cell wall with proinflammatory cascades. Intact PCho-containing cell wall binds to PAFr and is taken up into many cell types and causes various host cell responses. Simpler peptidoglycan lacking PCho binds to TLR2 while muramyl peptides ligate NOD proteins. This creates a hierarchy of responses to cell wall components based on size and PCho decoration. Asterisk PCho moiety; plus sign and; minus sign presence or absence of inflammatory activity (see [21])