Z-IETD-FMK clinical trial genitalium strains grown attached to plastic cultureware [31]. These phenomena suggest that M. genitalium attachment to and invasion of reproductive tract ECs may not require a well-defined tip structure. In addition, attachment and invasion may involve cellular receptors that are localized to specific membrane sites that

are better modeled using polarized 3-dimensional EC cultures. Indeed, the observed egress of M. genitalium from infected mucosal ECs likely would lead to infection C59 wnt solubility dmso of an adjacent cells in vivo rather than into the culture supernatant of traditional 2-dimensional cultures. This considered, a 3-dimensional multi-layer model of vaginal EC infection might better address how M. genitalium interacts with the host mucosa and establishes primary reproductive tract infection. Because ECs likely serve as the first responders to STI, we investigated the acute-phase cytokine

response to M. genitalium from human vaginal and cervical ECs. We found that M. genitalium elicited minimal innate responses from human vaginal ECs from 3 donors but ecto- and endocervical ECs were highly responsive and secreted cytokines consistent with recruitment of immune cells selleck compound including IL-8, G-CSF, GM-CSF and MCP-1 (Table 1). The increased responsiveness of endocervical ECs may have biological relevance, as the normally sterile upper tract tissues likely are more sensitive to microbial contamination than the lower genital tract. Paradoxically, it is in the upper tract tissues where inflammation due to microbial infection likely has the most severe consequences potentially leading to

PID, salpingitis or reduced fertility [36]. Our studies were focused primarily on the lower genital tract but the heightened sensitivity of endocervical ECs provides rationale for testing cell types of the upper tract including endometrial [35] and fallopian ECs. All of the cell types used for cytokine analysis were immortalized by transduction of the human papilloma virus E6/E7 genes known to reduce the levels, but preserve the pattern of cytokine secretion relative to primary progenitor cells [16]. Therefore, we are confident that the observed cytokine inductions indicate the character of the responses but likely underestimate the actual levels of secretion. Considering the profile of secreted cytokines by M. genitalium-infected reproductive Cyclooxygenase (COX) ECs, we next investigated whether macrophages could play a role in the cellular immune response to M. genitalium. Following exposure to human MDM, phagocytosis of M. genitalium occurred rapidly (Figure 3) resulting in complete ablation of bacterial viability by 6 h PI. Importantly, several key pro-inflammatory cytokines were induced in response to M. genitalium exposure. IL-6 secretion may be of particular importance considering that IL-6 from vaginal secretions is positively correlated with HIV-1 burden [14] and known to up-regulate HIV-1 replication [15]. Indeed, the microbial burden of M.