Loren H. Hoffman

The mechanisms by which Neisseria meningitidis establishes a carrier state or invades mucosal surfaces of the host to cause septicemia and meningitis are unknown. An experimental model of human columnar nasopharyngeal tissue in organ culture was developed, and the interaction of encapsulated, piliated N meningitidis with this mucosal surface was studied. Electron microscopic studies showed that meningococci attached selectively to nonciliated columnar cells of the nasopharynx. After attachment, the microvilli of these nonciliated cells elongated and surrounded the organisms. Six to twelve hours after infection, endocytic vacuoles containing meningococci were seen in the apical portion of some nonciliated columnar cells. Later, diplococci were seen in the subepithelial tissues adjacent to lymphoid tissue; this observation suggested that meningococci had penetrated the epithelial layer. The interaction of meningococci with the nasopharyngeal epithelium may be an important means whereby these bacteria establish a carrier state or invade the host.

Neisseria gonorrhoeae are transported across the mucosa of human fallopian tubes in organ culture by mucosal cells. The steps in this process are (1) attachment of gonococci to microvilli of nonciliated cells, (2) phagocytosis of gonococci by these cells, (3) transport of phagocytic vacuoles containing gonococci to the base of the cell, and (4) exocytosis of gonococci with phagocytic vacuoles into the subepithelial tissues. In vivo gonococci in the subepithelial tissues may cause extensive local disease (e.g., salpingitis) or invade blood vessels to cause disseminated disease. Preliminary studies of human nasopharyngeal tissue in organ culture infected with Neisseria meningitidis indicate that meningococci attach to microvilli of nonciliated cells and are phagocytized by these cells. They subsequently appear in subepithelial tissues, but the route they take is not yet certain. These observations suggest that the mechanisms of attachment to and penetration of fallopian tube and nasopharyngeal mucosa by N. gonorrhoeae and N. meningitidis are similar or possibly identical.

Mammalian uteri are unreceptive to blastocyst implantation except during a relatively brief period. The transmembrane, cell surface mucin, Muc1, is present on epithelial cells of nonreceptive uteri in various species and has been demonstrated to have antiadhesive properties. These activities of Muc1 may prevent interaction of the embryonic trophoblast cells with the uterine epithelium. A previous study indicated that Muc1 expression in the rabbit, as in primates, is up-regulated by progesterone. This response would be expected to create a nonadhesive uterine surface during the progesterone-dominated receptive phase. In the current study, Northern blot analysis was used to evaluate Muc1 messenger RNA expression in the endometrium of estrous and progesterone-treated estrous rabbits and in endometrium from different stages of pregnancy or pseudopregnancy. Steady state levels of Muc1 messenger RNA were increased 10-fold when estrous animals were treated with progesterone for 5 days. Muc1 message was elevated 2- to 6-fold over estrous levels in endometrium of pseudopregnant females and 30-fold in preimplantation stage (6.75 days postcoitum) uteri. During implantation (7.25 day postcoitum), the high level of Muc1 expression continued in nonimplantation regions, but was dramatically reduced in endometrium from implantation sites. Using immunofluorescence localization, Muc1 protein was present on the apical surface of epithelial cells of estrous, pseudopregnant (4 and 6.75 days), preimplantation (6.75 days), and implantation (7.25 day) stage uteri. At the latter stage, luminal epithelium apposed to blastocysts had a marked reduction or absence of Muc1 immunostaining. Muc1-immunoreactive cells included luminal and cryptal epithelium in pregnant/pseudopregnant uteri, whereas the glandular cells stained weakly. Short term coculture of uterine epithelial cells with trophoblastic vesicles derived from 6.75-day blastocysts also resulted in a local reduction in apical epithelial Muc1 staining. These findings demonstrate that Muc1 expression is up-regulated by progesterone in the rabbit uterine epithelium and increases incrementally during pre- and periimplantation stages. Removal of Muc1 from the epithelial surface at implantation sites is accomplished locally via signals apparently produced by the blastocyst.