Patterns of pathogenesis: discrimination of pathogenic and nonpathogenic microbes by the innate immune system

Abstract

The dominant conceptual framework for understanding innate immunity has been that host cells respond to evolutionarily conserved molecular features of pathogens called pathogen-associated molecular patterns (PAMPs). Here, we propose that PAMPs should be understood in the context of how they are naturally presented by pathogens. This can be experimentally challenging, since pathogens, almost by definition, bypass host defense. Nevertheless, in this review, we explore the idea that the immune system responds to PAMPs in the context of additional signals that derive from common "patterns of pathogenesis" employed by pathogens to infect, multiply within, and spread among their hosts.

Figure 1. Dual Recognition of PAMPs

A highly simplified schematic of the responses to three PAMPs is shown. PAMPs are often sensed in different subcellular compartments, or in different cell types, leading to distinct responses. Thus, host cells not only sense whether a PAMP is present but also sense when and where the PAMP is present.

Figure 2. Patterns of Pathogenesis

Live pathogens commonly employ a small number of strategies to infect, replicate within, and spread among their hosts. These strategies appear to be detected as unique patterns by the host, leading to specific immune responses that discriminate pathogenic and non-pathogenic microbes.