Grant: Project Grant

Neisseria gonorrhoeae (Ngo) is a bacterial pathogen that causes more than 100 million cases of the sexually-transmitted disease gonorrhea in the world each year. In addition to the copious male urethral or female endocervical discharge that are the hallmark of gonorrhea, Ngo infections can progress to cause scarring of the reproductive tract, chronic pelvic pain and dangerous ectopic pregnancies in women, or blindness of children born to infected mothers. Critically, Ngo has recently attained 'superbug' status because it has acquired resistance to all clinically relevant oral and injectable antibiotics, making the threat of untreatable gonorrhea a looming reality. This has led to a global urgency to develop new strategies to halt the spread of Ngo and/or to treat established infections caused by this dangerous microbe. It is clear that the damage associated with Ngo infection is caused by an overzealous response of a single type of white blood cell, known as the neutrophil. What is disconcerting is that the neutrophil is the immune system's most potent bacterial-killing immune cell type, yet the massive numbers of neutrophils that enter Ngo-infected tissues are not capable of clearing the infection. Moreover, the neutrophil response is clear evidence that the immune system has been alerted to the presence of a dangerous bacterial intruder, yet it does not develop an effective immune 'memory' response that would otherwise protect against subsequent infections. Notably, recent work has revealed that different types of neutrophils exist, with functions ranging from the promotion of inflammation to the suppression of effective immune responses. This paradigm-shifting finding clearly contradicts the classical belief that all neutrophils are the same. Our research plan aims to describe what type of neutrophils are recruited to Ngo-infected tissues, and then to develop new strategies to elicit a response that will effectively combat gonococcal infection and diseas