Figure 4.

NETs in UTIs and STDs. (A) During UPEC infection, bacteria interact with bladder epithelial and immune cells of the urogenital epithelium through TLRs, NLRs and uroplakin-1a, which leads to the production of proinflammatory cytokines that induce neutrophil migration to site. Neutrophils release extracellular traps with antimicrobial peptides, such as citrullinated histones, elastase, MPO, proteinase 3 and cathepsin G, which eliminate the infection. (B) In C. albicans infection, epithelial cells secrete cytokines that act as neutrophil chemoattractants; neutrophils recognize this pathogen through CR3 or dectin-2 receptors, which induce NET release. Calprotectin, a protein associated with the DNA of extracellular traps, possesses antifungal activity which aids in the infection clearance. However, other bacteria, such as C. trachomatis and N. gonorrhoeae, have evasion mechanisms characterized by secreting factors, such as the protein CPAF, and the enzymes Nuc and Lpta, respectively, which prevent degranulation and cytokine release, degrade NET components and inhibit ROS-dependent pathways for their release. UTIs, urinary tract infections; STDs, sexually transmitted diseases; NET, neutrophil extracellular trap; MPO, myeloperoxidase; LptA, LOS phosphoethanolamine transferase A; CPAF, Chlamydial Protease-like Activating Factor; TLR, Toll-like receptor; NLR, NOD-like receptor; IL-1, interleukin-1; IL-6, interleukin-6; IL-8, interleukin-8; TNF-α, tumor necrosis factor-α. Created with BioRender.com.