Yersina perstis interactions with macrophages

Plague, an emerging infectious disease endemic to multiple continents, including North and South America, is a top priority in national biodefense. Studying pathogenic yersiniae, the bacteria responsible for plague, provides valuable insights into pathogenesis and evolution. Genomic sequencing of the Yersinia genus and extensive Yersinia pestis genomes spanning from the Bronze Age to the present offer a rich resource for this research. A distinct feature of plague infections is the lack of inflammation at bacterial replication sites. Recent studies on pneumonic plague reveal a two-phase course: a delayed inflammatory response followed by a highly inflammatory phase as the disease progresses. In the initial phase, non-human primate and mouse models show no cellular infiltration. Extracellular presence of Y. pestis in primate lungs does not trigger inflammation. In a rat model of bubonic plague, neutrophil infiltration into draining lymph nodes is delayed, and infected sites undergo necrosis instead of inflammation. Comparisons between Y. pseudotuberculosis and Y. pestis infections demonstrate neutrophil recruitment but inadequate containment of the infection. Research on the type III secretion system and other virulence factors has explored their role in neutralizing early inflammatory responses. However, understanding macrophage polarization during early plague stages remains incomplete. A central hypothesis suggests that Y. pestis prevents inflammation by inhibiting M1 polarization or inducing M2 macrophages Investigating these mechanisms will enhance knowledge of how macrophage polarization contributes to early immune suppression in plague, preventing the infiltration of polymorphonuclear leukocytes (PMNs) and promoting the initial anti-inflammatory stage of plague. Aim 1. Investigate macrophage polarization after Yersinia pestis exposure to block inflammation by either inhibiting M1 polarization or inducing M2 macrophages. Aim 2. Determine signaling pathways induced and mechanisms used by Y. pestis to influence macrophage polarization. Aim 3. Examine the virulence factors utilized by Y. pestis to polarize macrophages.