Expression of Proinflammatory Cytokines and Receptors by Human Fallopian Tubes in Organ Culture following Challenge withNeisseria gonorrhoeae

Abstract

Infection of the Fallopian tubes (FT) byNeisseria gonorrhoeae can lead to acute salpingitis, an inflammatory condition, which is a major cause of infertility. Challenge of explants of human FT with gonococci induced mRNA expression and protein secretion for the proinflammatory cytokines interleukin (IL)-1␣, IL-1␤, and tumor necrosis factor alpha (TNF-␣) but not for granulocyte-macrophage colony-stimulating factor. In contrast, FT expression of IL-6 and of the cytokine receptors IL-6R, TNF receptor I (TNF-RI), and TNF-RII was constitutive and was not increased by gonococcal challenge. These studies suggest that several proinflammatory cytokines are likely to contribute to the cell and tissue damage observed in gonococcal salpingitis.

Regulatory T Cells Are Locally Induced during Intravaginal Infection of Mice withNeisseria gonorrhoeae

“…Overall, primary cell and organ culture systems have been successfully developed to examine the initial phase of gonococcal pathogenesis (9,10,13,29,48) where several gonococcus membrane components, such as Pil and Opa, are highly relevant (30). However, the mechanisms explaining why female infection occurs in a high number of cases without inflammatory signs, with low levels of antibody induction, and with no disease resolution responses are not understood.…”

Mucosal Immunity and Evasion Strategies of Neisseria gonorrhoeae

“…IL-17 plays a particularly significant role in regulating neutrophils (PMNn) recruitment and granulopoiesis via the production of IL-8 and MIP-2 (CXCL2) (Laan et al, 1999). In early stages of infections, interactions between N. gonorrhoeae and epithelial mucosa trigger immune response with release of IL-1, IL-6, IL-8 and TNF which serve to recruit and activate PMNn to the site of infection and promoting their bactericidal activity limiting bacterial penetration into submucosal tissues (Fisette et al, 2003;Maisey et al, 2003;McGee et al, 1999). In men, PMNs appear in urethral swabs and urine several days after infection and immediately prior to the onset of symptoms (Cohen and Cannon, 1999).…”

Nitric oxide is not involved in Neisseria gonorrhoeae-induced cellular damage of human Fallopian tubes in vitro

“…An exclusion criterion was the occurrence of sexually transmitted disease during the last year or a history of pelvic inflammatory disease. FT was processed immediately after removal, as described previously [Maisey, 2003]. Briefly, the muscle layer was dissected and discarded and the remaining mucosa was cut with a surgical blade into segments of 1 cm 2 and placed in Dulbecco's modified Eagle's medium (DMEM; Hyclone, Utah, USA) in culture plates.…”

“…Previously, we identified the expression of multiple pro-inflammatory cytokines such as interleukin IL-1α, IL-1β and IL-6 in FT explants infected with Ngo [Maisey et al, 2003]. These cytokines and TNF-α are likely to play important roles in the innate defence of the FT, principally enhancing leukocytosis and oxidative respiratory burst responses [Dinarello, 2002] by means of production of reactive oxygen and nitrogen species such as nitric oxide (NO) [Busse and Mulsch, 1990;Kleinert et al, 2003;Thiemermann et al, 1993].…”