Project 2 - ABSTRACT The work proposed in this study seeks to investigate the role of macrophages colonization by Neisseria gonorrhoeae (N.g) during infection and the impact on gonorrhea development. Because N.g is a highly human adapted pathogen, it has developed numerous mechanisms to avoid and actively suppress innate and adaptive immune responses. Macrophages are present in significant numbers throughout the genitourinary mucosae and represent about 10% of total number of leukocytes recovered from these tissues. Thus, it?s likely that N.g encounters these cells during infection and that macrophages play an important role in N.g pathogenesis. We uncovered that N.g colonizes and establishes topologically distinct colonies in macrophages. During colonization N.g manipulates the actin cytoskeleton to create an intracellular niche supportive of bacterial replication. This new model of N.g persistence in macrophages is significant for gonorrhea symptomatology and outcome, since the relevant cellular reservoir of bacteria during in vivo infections has yet to be identified. Therefore, we hypothesize that N.g colonizes and alters the macrophages immune response in order to establish persistent growth within its host. In the first aim of this proposal we will investigate the transcriptional changes that occur in the infected cell and the bacterium during N.g colonization of macrophages. In the second aim we will assess the presence and the function of macrophages in a mouse model of N.g infection.
