Reduced Uterine Tissue Damage during Chlamydia muridarum Infection in TREM-1,3-Deficient Mice

Abstract

Genital infections with Chlamydia trachomatis can lead to uterine and oviduct tissue damage in the female reproductive tract. Neutrophils are strongly associated with tissue damage during chlamydial infection, while an adaptive CD4 T cell response is necessary to combat infection. Activation of triggering receptor expressed on myeloid cells-1 (TREM-1) on neutrophils has previously been shown to induce and/or enhance degranulation synergistically with TLR-signaling. Additionally, TREM-1 can promote neutrophil transepithelial migration. In this study, we sought to determine the contribution of TREM-1,3 in immunopathology in the female mouse genital tract during Chlamydia muridarum infection. Relative to control mice, trem1,3 -/- mice had no difference in chlamydial burden or duration of lower genital tract infection. We also observed a similar incidence of oviduct hydrosalpinx 45 days post-infection in trem1,3 -/- compared to WT mice. However, compared to WT, trem1,3 -/- mice developed significantly fewer uterine horn hydrometra. Early in infection, trem1,3 -/- mice displayed a notable decrease in the number of uterine glands containing polymorphonuclear cells and uterine horn lumens had fewer neutrophils, with increased G-CSF. Trem1,3 -/- mice also had reduced erosion of the luminal epithelium. These data indicate TREM-1,3 contributes to transepithelial neutrophil migration in the uterus and uterine glands, promoting the development of uterine hydrometra in infected mice.

Single-Cell RNA Sequencing Reveals Transcriptional Landscape of Neutrophils and Highlights the Role of TREM-1 in EAE

“…Studies have demonstrated that TREM-1 exerts a central role in modulating inflammatory signaling and facilitating neutrophil transepithelial migration into diverse settings such as the alveolar airspace, uterus, and uterine glands. 59 , 60 We put forth the hypothesis that TREM-1 facilitates the migration of neutrophils to CLNs, where neutrophils exert diverse effects, and inhibiting TREM-1 could potentially curtail neutrophil migration. As anticipated, LR12 exhibited the capacity to curtail neutrophil infiltration into CLNs during the acute stage of EAE and impede HL-60 cell migration.…”

Epidemiological analysis of hydrometra and its predictive value in gynecological tumors

“…In addition, McQueen etal. ( 27 ) reported that increased triggering receptor expressed on myeloid cells 1/3 (TREM-1/3) infected mice through promoting transepithelial neutrophil migration in the uterus and uterine glands. However, most current studies have focused on animals, with limited data from humans.…”