The dynamic influence of commensal bacteria on the immune response to pathogens

Abstract

Alterations in the composition of commensal bacterial communities are associated with enhanced susceptibility to multiple inflammatory, allergic, metabolic and infectious diseases in humans. In the context of infection, commensal bacteria-derived signals can influence the host immune response to invasive pathogens by acting as an adjuvant to boost the immune response to infection or by providing tonic stimulation to induce basal expression of factors required for host defense. Conversely, some pathogens have evolved mechanisms that can utilize commensal bacteria to establish a replicative advantage within the host. Thus, examining the dynamic relationship that exists between the mammalian host, commensal bacteria and invasive pathogens can provide insights into the etiology of pathogenesis from an infection.

Figure 1. Dynamic host – commensal bacteria – pathogen interactions in the intestinal microenvironment

Intestinal commensal bacteria communities limit intestinal infection by (1) competing for space and resources or (2) stimulating intestinal epithelial and immune cells. Epithelial cells can produce anti-microbial peptide, such as RegIIIγ, that inhibit colonization of invasive bacteria. Resident innate immune cells can secrete cytokines that activate host-defense defense mechanisms and shape the quality and magnitude of the adaptive immune response to infection. Conversely, (3) some intestinal pathogens have evolved to utilize commensal bacterial-derived signals to improve infectivity.

Figure 2. Commensal bacteria-derived signals calibrate responsiveness of peripheral immune cells

Commensal bacteria can basally stimulate peripheral immune cells, eliciting epigenetic modification in host defense genes and maintaining these genes in an open, transcriptionally active state. Commensal bacteria may (1) directly, via translocation of commensal bacteria-derived products, or (2) indirectly, via stimulation of intestinal epithelial cells or resident immune cells to secrete factors into the circulation, modulate peripheral immune cells. This tonic stimulation by commensal bacteria facilitates rapid responsiveness by immune cells upon encounter with a pathogen.