Proinflammatory Cytokine and Nitric Oxide Production by Human Macrophages Stimulated with Trichomonas vaginalis

Abstract

Trichomonas vaginalis commonly causes vaginitis and perhaps cervicitis in women and urethritis in men and women. Macrophages are important immune cells in response to T. vaginalis infection. In this study, we investigated whether human macrophages could be involved in inflammation induced by T. vaginalis. Human monocyte-derived macrophages (HMDM) were co-cultured with T. vaginalis. Live, opsonized-live trichomonads, and T. vaginalis lysates increased proinflammatory cytokines, such as TNF-alpha, IL-1beta, and IL-6 by HMDM. The involvement of nuclear factor (NF)-kappaB signaling pathway in cytokine production induced by T. vaginalis was confirmed by phosphorylation and nuclear translocation of p65 NF-kappaB. In addition, stimulation with live T. vaginalis induced marked augmentation of nitric oxide (NO) production and expression of inducible NO synthase (iNOS) levels in HMDM. However, trichomonad-induced NF-kappaB activation and TNF-alpha production in macrophages were significantly inhibited by inhibition of iNOS levels with L-NMMA (NO synthase inhibitor). Moreover, pretreatment with NF-kappaB inhibitors (PDTC or Bay11-7082) caused human macrophages to produce less TNF-alpha. These results suggest that T. vaginalis stimulates human macrophages to produce proinflammatory cytokines, such as IL-1, IL-6, and TNF-alpha, and NO. In particular, we showed that T. vaginalis induced TNF-alpha production in macrophages through NO-dependent activation of NF-kappaB, which might be closely involved in inflammation caused by T. vaginalis.

Involvement of purinergic signaling on nitric oxide production by neutrophils stimulated with Trichomonas vaginalis

“…Park et al [14] showed that macrophage cytotoxicity against T. vaginalis is regulated by NO, with inhibition of trichomonicidal activity after macrophages exposure to L-NMMA. In other work, the parasites induced macrophage to produce proinflammatory cytokines, such as IL-1, IL-6, TNF-α, and NO, via NF-κB [37]. In vivo, it was observed the increase in polymorphonuclears (PMNs), vaginal epithelial cells, and reactive nitrogen intermediate (RNI) levels in mice infected with isolates from symptomatic patients as compared to asymptomatic subjects [38].…”

Differential Regulation of Proinflammatory Cytokine Expression by Mitogen-Activated Protein Kinases in Macrophages in Response to Intestinal Parasite Infection

“…Extensive reports have shown that common protozoan pathogens, such as T. cruzi, E. histolytica, T. vaginalis, and Leishmania, cause upregulation of proinflammatory cytokines to induce immune responses (46)(47)(48)(49). Macrophages, the first cells that encounter pathogens that cross the intestinal epithelium, may be resident in strategic locations, such as the lamina propria, or may be recruited to the inflamed gut by chemokine signals (38,50).…”

SNAP23-Dependent Surface Translocation of Leukotriene B 4 (LTB 4 ) Receptor 1 Is Essential for NOX2-Mediated Exocytotic Degranulation in Human Mast Cells Induced by Trichomonas vaginalis-Secreted LTB 4

“…In addition, TvSP induce intracellular reactive oxygen species (ROS) generation and apoptosis of human neutrophils (13,14). Infection with T. vaginalis is clinically important and linked to an increased incidence of human immunodeficiency virus type 1 transmission, preterm delivery, low birth weight, and cervical cancer (11)(12)(13). However, the signaling mechanism of TvSP-induced inflammatory responses at the mucosal tissues infected with T. vaginalis is not fully understood.…”

“…It is evident that TvSP directly stimulate various immune cells to perform various functions. For example, TvSP stimulate human neutrophils to produce the proinflammatory cytokines and chemokine, leading to the recruitment of various inflammatory cells (11,12). In addition, TvSP induce intracellular reactive oxygen species (ROS) generation and apoptosis of human neutrophils (13,14).…”