Underlying mechanisms for the transition of Listeria monocytogenes from pathogenesis to commensalism

Abstract

DoctorThe gastrointestinal tract harbors a dynamic and complex community of microorganisms, collectively known as commensal microbiota that is a key factor for the maintenance of gut homeostasis and health. Among gut microbiota, specific species have pathogenic potential to induce apparent damage to the host and intestinal inflammation under environmental or host pressure. In addition, environmental pathogens can adapt to occupy the host niches in the gut by inducing transient and limited pathogenesis during the co-evolution of host-microbe interactions. However, the specific underlying mechanism about how host immune factors permit commensalism of pathobionts or pathogens under steady-state conditions is not clearly understood. In this study, I aimed to investigate the underlying mechanisms for the transition of Listeria monocytogenes from pathogenesis to commensalism and to identify the immunological factors involved in the commensalism of L. monocytogenes. In the first part of this study, I demonstrated that a food-borne pathogen L. monocytogenes can establish commensalism in germ-free (GF) mice. Although enteric L. monocytogenes infection generated adequate systemic and intestinal tissue-resident CD8+ memory T cells in both GF and SPF mice to resolve the infection, GF mice were unable to eliminate L. monocytogenes in the lumen, which failed to infiltrate through intestinal epithelium and to induce chronic infection. In the second part, I revealed the underlying mechanisms by which immunological factors mediate the commensalism of L. monocytogenes. I found that innate immunity such as an antimicrobial peptide, especially Reg3, did not establish the commensalism of L. monocytogenes, whereas Reg3 gamma provided protective function against L. monocytogenes. On the other hand, L. monocytogenes-specific CD8+ T cells were sufficient to protective function against L. monocytogenes infection as well as promote the commensalism of L. monocytogenes in GF mice through the reversible down-regulation of virulence gene expression. In conclusion, these results suggest one of the possible mechanism how host immune factors permit the commensalism of pathogens. These results provide important insights into the host-microbe interaction and have implications for developing therapeutics against immune disorders induced by intestinal pathogens or pathobionts