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Global Analysis of Neutrophil Responses to Reveals a Self-Propagating Inflammatory Program


Gonorrhea is a sexually transmitted infection caused by the bacteria Neisseria gonorrhoeae. These bacteria have re-emerged as a public health priority due to its acquisition of resistance to multiple antibiotics, leading to fears of untreatable infection. The symptoms of gonorrhea include an intense inflammatory response that may lead to pus discharged from the infected genital tract and scarring of the reproductive tract caused by neutrophils recruited to the site of infection. Past studies have detailed molecular interactions that lead to neutrophil binding and engulfment of N. gonorrhoeae, yet it remains unclear why N. gonorrhoeae elicits such a pathogenic inflammatory response. In this study, we reveal that N. gonorrhoeae binding to the human innate decoy receptor, CEACAM3, elicits a potent intracellular signaling cascade that leads to neutrophil expression of cytokines that actively recruit other neutrophils to the infected tissues. As they encounter the gonococci, the next wave of neutrophils becomes similarly activated, leading to the progressive expansion in phagocytic cell numbers until they overwhelm the infected tissues. While this process promotes a rapid response to a troubling pathogen early during infection, the unrestrained recruitment of neutrophils and their toxic antimicrobial arsenal also lead to the pathogenic consequences associated with gonorrhea.


Vyšlo v časopise: Global Analysis of Neutrophil Responses to Reveals a Self-Propagating Inflammatory Program. PLoS Pathog 10(9): e32767. doi:10.1371/journal.ppat.1004341
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004341

Souhrn

Gonorrhea is a sexually transmitted infection caused by the bacteria Neisseria gonorrhoeae. These bacteria have re-emerged as a public health priority due to its acquisition of resistance to multiple antibiotics, leading to fears of untreatable infection. The symptoms of gonorrhea include an intense inflammatory response that may lead to pus discharged from the infected genital tract and scarring of the reproductive tract caused by neutrophils recruited to the site of infection. Past studies have detailed molecular interactions that lead to neutrophil binding and engulfment of N. gonorrhoeae, yet it remains unclear why N. gonorrhoeae elicits such a pathogenic inflammatory response. In this study, we reveal that N. gonorrhoeae binding to the human innate decoy receptor, CEACAM3, elicits a potent intracellular signaling cascade that leads to neutrophil expression of cytokines that actively recruit other neutrophils to the infected tissues. As they encounter the gonococci, the next wave of neutrophils becomes similarly activated, leading to the progressive expansion in phagocytic cell numbers until they overwhelm the infected tissues. While this process promotes a rapid response to a troubling pathogen early during infection, the unrestrained recruitment of neutrophils and their toxic antimicrobial arsenal also lead to the pathogenic consequences associated with gonorrhea.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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