No abstract

Metacyclic Leishmania promastigotes (PM), transmitted by sand-fly bite, are likely to interact initially with cells of the dendritic cell (DC) lineage(s) in the epidermis or dermis. Epidermal Langerhans cells internalize L. major amastigotes (AM) and transport them to draining lymph nodes (Moll, H., Fuchs, H., Blank, C. and Röllinghoff, M., Eur. J. Immunol. 1993. 23: 1595) but little is known about the interaction of DC with PM. The present study demonstrates that DC are able to internalize PM and that the fate of the parasites within DC differs from that within macrophages (M ¤). DC took up small numbers of PM which did not differentiate into AM but appeared to be degraded; M ¤ internalized large numbers of PM into parasitophor-ous vacuoles where they differentiated into AM. In response to direct stimulation with PM, DC from both C3H ("resistant" to L. major infection) and BALB/c ("susceptible") up-regulated production of IL-12 p40. In contrast, IL-12 production by M ¤ was not detected. DC exposed to either metacyclic PM or PM culture supernatants were also able to stimulate proliferative responses in lymph node T cells from naive mice. These data indicate that DC have the capacity to promote protective Th1 immune responses in Leishmania infection and suggest that DC exposed to PM may be useful in immunotherapy and vaccination.

Knowing the prevalence of potential etiologic agents of nongonococcal and nonchlamydial cervicitis is important for improving the efficacy of empirical treatments for this commonly encountered condition. We describe four multiplex PCRs (mPCRs), designated VDL05, VDL06, VDL07, and VDL09, which facilitate the detection of a wide range of agents either known to be or putatively associated with cervicitis, including cytomegalovirus (CMV), enterovirus (EV), Epstein-Barr virus (EBV), varicella-zoster virus (VZV), herpes simplex virus type 1 (HSV-1), and herpes simplex virus type 2 (HSV-2) (VDL05); Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma genitalium, and Mycoplasma hominis ( Cervicitis, an acute or chronic inflammation of the uterine cervix, is generally viewed as a consequence of infection with sexually transmissible agents. Neisseria gonorrhoeae and Chlamydia trachomatis are the most commonly reported pathogens, possibly because they are most frequently screened for. However, the etiology of most cases is undetermined and could be multifactorial in nature (11,34,35,40). Studies undertaken in other epidemiologic settings indicate significant differences in the prevalences of other cervical infectious agents (1,41,44,45,58). An underappreciation of the prevalences of and roles played by these nongonococcal and nonchlamydial agents potentially jeopardizes the effectiveness of empirical treatments for cervicitis. Unresolved cervicitis can result in ascending infection, endometritis, pelvic inflammatory disease, and salpingitis (11,23,46). Furthermore, cervicitis may enhance human immunodeficiency virus susceptibility by the disruption of mucosa, allowing increased viral replication within recruited inflammatory cells (30). The development of molecular methods, such as PCR and DNA hybridization, has allowed the detection of a range of agents whose etiologic roles in genital infections need to be further investigated, including the viruses cytomegalovirus (CMV), herpes simplex virus type 1 (HSV-1) and HSV-2 (4, 43), adenovirus (6,10,50), and the Mollicutes Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma hominis, and Mycoplasma genitalium (1,28,59). There have also been reports of genital infections caused by Epstein-Barr virus (EBV) (4, 55), varicella-zoster virus (VZV) (27), and enterovirus (EV) (24). We report here the use of four multiplex PCR (mPCR) assays, designated VDL05, VDL06, VDL07, and VDL09, based on a conventional platform, for the detection of 19 microorganisms in cervical swabs, including Treponema pallidum and C. trachomatis, Trichomonas vaginalis, group B streptococci, and five adenovirus species, in addition to those mentioned above. The assays were developed using cervical swabs from different women taken on one or more occasions during different visits to a sexual-health clinic. MATERIALS AND METHODSPatients. Cervical swabs (n ϭ 233) were taken from 175 women consecutively attending a sexual-health clinic in Sydney, Australia (between one and three visits), during 2006 and 2007 who we...

Activation of factor XI (FXI) by thrombin in vivo plays a role in coagulation by providing an important positive feedback mechanism for additional thrombin generation. FXI is activated in vitro by thrombin, or FXIIa in the presence of dextran sulfate. In this report, we investigated the effect of ␤2-glycoprotein I (␤2GPI) on the activation of FXI. ␤2GPI bound FXI in vitro and inhibited its activation to FXIa by thrombin and FXIIa. The affinity of the interaction between ␤2GPI and FXI was equivalent to the interaction between FXI and high molecular weight kininogen. Inhibition of FXI activation occurred with lower concentrations of ␤2GPI than found in human plasma. Proteolytic clipping of ␤2GPI by plasmin abolished its inhibition of FXI activation. The results suggest a mechanism of regulation whereby physiological concentrations of ␤2GPI may attenuate thrombin generation in vivo by inhibition of FXI activation. Plasmin cleavage of ␤2GPI provides a negative feedback that counteracts its inhibition of FXI activation.