Abstract
Being generally regarded as commensal bacteria, the pro-inflammatory capacity of Ureaplasma species has long been debated. Recently, we confirmed Ureaplasma–driven pro-inflammatory cytokine responses and a disturbance of cytokine equilibrium in primary human monocytes in vitro. The present study addressed the expression of CC chemokines and matrix metalloproteinase-9 (MMP-9) in purified term neonatal and adult monocytes stimulated with serovar 8 of Ureaplasma urealyticum (Uu) and serovar 3 of U. parvum (Up). Using qRT-PCR and multi-analyte immunoassay, we assessed mRNA and protein expression of the monocyte chemotactic proteins 1 and 3 (MCP-1/3), the macrophage inflammatory proteins 1α and 1β (MIP-1α/β) as well as MMP-9. For the most part, both isolates stimulated mRNA expression of all given chemokines and MMP-9 in cord blood and adult monocytes (p<0.05 and p<0.01). These results were paralleled by Uu and Up-induced secretion of MCP-1 protein in both cells (neonatal: p<0.01, adult: p<0.05 and p<0.01). Release of MCP-3, MIP-1α, MIP-1β and MMP-9 was enhanced upon exposure to Up (neonatal: p<0.05, p<0.01 and p<0.001, respectively; adult: p<0.05). Co-stimulation of LPS-primed monocytes with Up increased LPS-induced MCP-1 release in neonatal cells (p<0.05) and aggravated LPS-induced MMP-9 mRNA in both cell subsets (neonatal: p<0.05, adult: p<0.01). Our results document considerable expression of pro-inflammatory CC chemokines and MMP-9 in human monocytes in response to Ureaplasma isolates in vitro, adding to our previous data. Findings from co-stimulated cells indicate that Ureaplasma may modulate monocyte immune responses to a second stimulus.
Highlights
The genital mycoplasmas Ureaplasma urealyticum and Ureaplasma parvum are among the smallest free living and self-replicating organisms
Detection of Ureaplasma spp. in the amniotic fluid (AF) or placental tissues has been causally related to histologic chorioamnionitis, abortion and preterm birth (PTB), both at gestational ages less than 30 weeks [7,8] andin moderate preterm infants [9,10]
The current study investigated Ureaplasma-induced CC chemokine responses in primary human monocytes and the expression of matrix metalloproteinase-9 (MMP-9), aiming to expand our understanding of Ureaplasma virulence
Summary
The genital mycoplasmas Ureaplasma urealyticum (serovars 2, 4, 5 and 7–13) and Ureaplasma parvum (serovars 1, 3, 6, 14) are among the smallest free living and self-replicating organisms. They lack a cell wall, have limited biosynthetic capacities and colonize mucosal surfaces of the genitourinary and respiratory tract [1]. Lower genital tract colonization has been described as an independent risk factor for intrauterine infection and preterm birth (PTB) (i.e., delivery < 37 weeks of gestation) [4,5,6]. In preterm and term neonates, Ureaplasma spp. may cause invasive diseases, such as pneumonia, sepsis and meningitis [11,12,13]. Epidemiologic studies indicate a role of prenatal and perinatal Ureaplasma infection in neonatal short and long-term morbidity, in the development of bronchopulmonary dysplasia (BPD) [12,14]
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