title: Activation of NOD receptors by Neisseria gonorrhoeae modulates the innate immune response.
abstract: NOD1 and NOD2 are members of the NOD-like receptor family of cytosolic pattern recognition receptors that recognize specific fragments of the bacterial cell wall component peptidoglycan. Neisseria species are unique amongst Gram-negative bacteria in that they turn over large amounts of peptidoglycan during growth. We examined the ability of NOD1 and NOD2 to recognize Neisseria gonorrhoeae, and determined the role of NOD-dependent signaling in regulating the immune response to gonococcal infection. Gonococci, as well as conditioned medium from mid-logarithmic phase grown bacteria, were capable of activating both human NOD1 and NOD2, as well as mouse NOD2, leading to the activation of the transcription factor NF-κB and polyubiquitination of the adaptor receptor-interacting serine-threonine kinase 2. We identified a number of cytokines and chemokines that were differentially expressed in wild type versus NOD2-deficient macrophages in response to gonococcal infection. Moreover, NOD2 signaling up-regulated complement pathway components and cytosolic nucleic acid sensors, suggesting a broad impact of NOD activation on innate immunity. Thus, NOD1 and NOD2 are important intracellular regulators of the immune response to infection with N. gonorrhoeae. Given the intracellular lifestyle of this pathogen, we believe these cytosolic receptors may provide a key innate immune defense mechanism for the host during gonococcal infection.
authors.affiliation: 1Section of Infectious Diseases, Department of Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Mavrogiorgos
authors.forename: Samrawit
authors.initials: S
authors.lastname: Mekasha
authors.forename: Yibin
authors.initials: Y
authors.lastname: Yang
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Kelliher
authors.forename: Robin R
authors.initials: RR
authors.lastname: Ingalls
mesh_terms: D000818:Animals; D003167:Complement Activation / Q000235:genetics; D006069:Gonorrhea / Q000276:immunology*; D057809:HEK293 Cells; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D056747:Immunomodulation; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D009344:Neisseria gonorrhoeae / Q000276:immunology*; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D010457:Peptidoglycan / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D000099317:Hippo Kinases
chemical_list: D016328:NF-kappa B; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D010457:Peptidoglycan; D017346:Protein Serine-Threonine Kinases; C481222:Slk protein, rat; D000099317:Hippo Kinases
keywords: Innate immunity; NOD-like receptors; Neisseria gonorrhoeae