Trichomonas vaginalis promotes apoptosis of human neutrophils by activating caspase‐3 and reducing Mcl‐1 expression

Abstract

Neutrophils are the predominant inflammatory cells found in the vaginal discharge of patients with Trichomonas vaginalis infection. However, it is not known whether neutrophil apoptosis is induced by live T. vaginalis. Therefore, we examined whether T. vaginalis can influence neutrophil apoptosis, and also whether caspase-3 and the Bcl-2 family members are involved in the apoptosis. Thus, human neutrophils were incubated with live T. vaginalis and neutrophil apoptosis was evaluated by Giemsa, annexin V-PI, and DiOC6 stainings. The neutrophil apoptosis was significantly higher in those incubated with T. vaginalis than in the control group. When trichomonads were pre-treated with mAb to AP65 (adhesin protein), or when trophozoites were separated from neutrophils using a Transwell chamber, neutrophil apoptosis was significantly reduced. The activation of caspase-3 was evident in neutrophils undergoing spontaneous apoptosis but was markedly enhanced during T. vaginalis-induced apoptosis. Moreover, the inhibition of caspase-3 effectively reduced T. vaginalis-induced apoptosis. Trichomonad-induced apoptosis was also associated with reduced expression of the neutrophil anti-apoptotic protein, Mcl-1. These results indicate that T. vaginalis alters Mcl-1 expression and caspase-3 activation, thereby inducing apoptosis of human neutrophils.

Delayed Human Neutrophil Apoptosis by Trichomonas vaginalis Lysate

“…At the site of trichomoniasis, clearance of aged or apoptotic neutrophils may help to protect normal tissues from the toxic molecules released by necrotic neutrophils. Our previous study suggested that live T. vaginalis increases neutrophil apoptosis; this may contribute to the resolution of inflammation via clearance of apoptotic neutrophils [12,13]. However, the T. vaginalis lysate used in this experiment decreases neutrophil apoptosis and may subsequently allow the initiation of inflammation.…”

“…Since live T. vaginalis induced neutrophil apoptosis via Mcl-1 and caspase-3 in our previous studies, we decided to examine Mcl-1 and caspase-3 in neutrophils to investigate the related mechanism of T. vaginalis lysate-induced delayed neutrophil apoptosis [12,13]. As shown in sate-co-incubated neutrophils was maintained after 25 hr of incubation and at the same time point caspase-3 cleavage was reduced compared with untreated neutrophils.…”

“…Cells were analyzed by Western blots using a previously described method to investigate the effect of Mcl-1 and caspase-3, key elements of the intrinsic mitochondrial pathway of apoptosis, on delaying neutrophil apoptosis induced by T. vaginalis lysate [12]. Mcl-1, an anti-apoptotic Bcl-2 protein, was maintained in T. vaginalis lysate-co-incubated neutrophils at 25 hr and decrea- sed after 38 hr incubation.…”

“…In our previous report, live T. vaginalis induced human neutrophil apoptosis via a caspase-3 and Mcl-1 dependent manner using reactive oxygen species (ROS) [12,13]. However, the relationship between T. vaginalis lysate and the apoptosis of human neutrophils is still unclear.…”

Mechanisms ofTritrichomonas foetusPathogenicity in Cats with Insights from Venereal Trichomonosis

“…Trichomonas vaginalis and bovine T. foetus infection are associated with endometrial inflammation characterized by the presence of neutrophils, plasma cells, and lymphocytes 97, 98. In in vitro, T. vaginalis has been shown to phagocytose leukocytes and induce apoptosis of neutrophils and macrophages 33, 99, 100. Moreover, T. vaginalis suppresses expression of the macrophage proinflammatory cytokines interleukin‐12 and tumor necrosis factor α (TNFα) by inhibition of nuclear factor kappa B (NF‐κB) activity, and enhances expression of anti‐inflammatory cytokines interleukin‐10 and tumor necrosis factor β (TNFβ) 101, 102.…”