ABSTRACT
Membrane-associated mucins (MAMs) expressed on the ocular surface epithelium form a dense glycocalyx that is hypothesized to protect the cornea and conjunctiva from external insult. In this study, the hypothesis that the MAMs MUC1 and MUC16, expressed on the apical surface of the corneal epithelium, suppress Toll-like receptor (TLR)-mediated innate immune responses was tested. Using an in vitro model of corneal epithelial cells that are cultured to express MAMs, we show that reduced expression of either MUC1 or MUC16 correlates with increased message and secreted protein levels of the proinflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) following exposure of cells to the TLR2 and TLR5 agonists, heat-killed Listeria monocytogenes and flagellin, respectively. As mice express Muc1 (but not Muc16) in the corneal epithelium, a Muc1(-/-) mouse model was used to extend in vitro findings. Indeed, IL-6 and TNF-α message levels were increased in the corneal epithelium of Muc1(-/-) mice, in comparison with wild-type mice, following exposure of enucleated eyes to the TLR2 and TLR5 agonists. Our results suggest that the MAMs MUC1 and MUC16 contribute to the maintenance of immune homeostasis at the ocular surface by limiting TLR-mediated innate immune responses.
Subject(s)
CA-125 Antigen/immunology , Conjunctiva/immunology , Cornea/immunology , Immunity, Innate , Membrane Proteins/immunology , Mucin-1/immunology , Toll-Like Receptor 2/immunology , Toll-Like Receptor 5/immunology , Animals , CA-125 Antigen/genetics , Cell Line, Transformed , Conjunctiva/microbiology , Cornea/microbiology , Cytokines/genetics , Cytokines/immunology , Humans , Listeria monocytogenes/immunology , Membrane Proteins/genetics , Mice , Mice, Knockout , Mucin-1/genetics , Toll-Like Receptor 2/genetics , Toll-Like Receptor 5/geneticsABSTRACT
This prospective in-vitro study evaluates the synergistic potential of various antibiotic combinations against resistant pathogens isolated from urinary tract infections (UTIs) in patients with diabetes mellitus. Antibiotic combinations using the microtiter checkerboard method showed that overall, synergy could be seen in 41.86%-67.44% cases amongst the five different antibiotic combinations studied against the four predominant resistant pathogens namely Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Klebsiella ozaenae. The checkerboard synergy studies showed that 69.23% of the S. aureus strains tested were synergistically inhibited by the combination of ofloxacin + cefotaxime [OF+CF], 83.33% of the E. coli strains and 75% of the K. ozaenae strains were synergistically inhibited by the combination of amikacin + cefotaxime [AK+CF], while 58.33% of the P. aeruginosa strains were synergistically inhibited by the combination of amikacin + piperacillin [AK+PP].