RESUMO
We present the case of a 39-year-old woman, G1P0, who had conceived twins via in-vitro fertilization, who presented at 27 weeks of gestation with nasal congestion and dry cough for 7 days. On presentation, her physical examination was benign, except for sinus tachycardia, and she was oxygenating adequately on room air. Laboratory studies were unremarkable, except a PCR test positive for SARS-COV2, and a CT scan of her chest showed bilateral multi-focal ground-glass opacities. A fetal non-stress test was reassuring. She was treated with intravenous fluids, ceftriaxone, azithromycin, and hydroxychloroquine. During her hospital stay, she developed progressively worsening respiratory failure, initially requiring non-invasive ventilation, and subsequently progressed to acute respiratory distress syndrome requiring mechanical ventilation. She then suffered from sudden hypoxemia and hemodynamic collapse, on maximal ventilatory support, prompting an emergency cesarean section at bedside. This led to rapid stabilization of hemodynamic parameters, and of her overall respiratory status. Both the twins were born prematurely, and one of them tested positive for SARS-COV2.
RESUMO
Toll-like receptors (TLRs) have recently been identified as fundamental components of the innate immune response to bacterial pathogens. We investigated the role of TLR signaling in immune defense of the mucosal epithelial cells of the lower female genital tract. This site provides first line defense against microbial pathogens while remaining tolerant to a complex biosystem of resident microbiota. Epithelial cells derived from normal human vagina, ectocervix, and endocervix expressed mRNA for TLR1, -2, -3, -5, and -6. However, they failed to express TLR4 as well as MD2, two essential components of the receptor complex for LPS in phagocytes and endothelial cells. Consistent with this, endocervical epithelial cells were unresponsive to protein-free preparations of lipooligosaccharide from Neisseria gonorrhoeae and LPS from Escherichia coli. However, they were capable of responding to whole Gram-negative bacteria and bacterial lysates, as demonstrated by NF-kappaB activation and proinflammatory cytokine production. The presence of soluble CD14, a high-affinity receptor for LPS and other bacterial ligands, enhanced the sensitivity of genital tract epithelial cells to both low and high concentrations of bacteria, suggesting that soluble CD14 can act as a coreceptor for non-TLR4 ligands. These data demonstrate that the response to N. gonorrhoeae and other Gram-negative bacteria at the mucosal surface of the female genital tract occurs in the absence of endotoxin recognition and TLR4-mediated signaling.