IgG in cervicovaginal mucus traps HSV and prevents vaginal herpes infections.

IgG is the predominant immunoglobulin in cervicovaginal mucus (CVM), yet how immunoglobulin G (IgG) in mucus can protect against infections is not fully understood. IgG diffuses rapidly through cervical mucus, slowed only slightly by transient adhesive interactions with mucins. We hypothesize that this almost unhindered diffusion allows IgG to accumulate rapidly on pathogen surfaces, and the resulting IgG array forms multiple weak adhesive crosslinks to mucus gel that effectively trap (immobilize) pathogens, preventing them from initiating infections. Here, we report that herpes simplex virus serotype 1 (HSV-1) readily penetrated fresh, pH-neutralized ex vivo samples of CVM with low or no detectable levels of anti-HSV-1 IgG but was trapped in samples with even modest levels of anti-HSV-1 IgG. In samples with little or no endogenous anti-HSV-1 IgG, addition of exogenous anti-HSV-1 IgG, affinity-purified from intravenous immunoglobulin, trapped virions at concentrations below those needed for neutralization and with similar potency as endogenous IgG. Deglycosylating purified anti-HSV-1 IgG, or removing its Fc component, markedly reduced trapping potency. Finally, a non-neutralizing IgG against HSV-gG significantly protected mice against vaginal infection, and removing vaginal mucus by gentle lavage abolished protection. These observations suggest that IgG-Fc has a glycan-dependent "muco-trapping" effector function that may provide exceptionally potent protection at mucosal surfaces.

MUC1 enhances invasiveness of pancreatic cancer cells by inducing epithelial to mesenchymal transition.

Increased motility and invasiveness of pancreatic cancer cells are associated with epithelial to mesenchymal transition (EMT). Snai1 and Slug are zinc-finger transcription factors that trigger this process by repressing E-cadherin and enhancing vimentin and N-cadherin protein expression. However, the mechanisms that regulate this activation in pancreatic tumors remain elusive. MUC1, a transmembrane mucin glycoprotein, is associated with the most invasive forms of pancreatic ductal adenocarcinomas (PDA). In this study, we show that over expression of MUC1 in pancreatic cancer cells triggers the molecular process of EMT, which translates to increased invasiveness and metastasis. EMT was significantly reduced when MUC1 was genetically deleted in a mouse model of PDA or when all seven tyrosines in the cytoplasmic tail of MUC1 were mutated to phenylalanine (mutated MUC1 CT). Using proteomics, RT-PCR and western blotting, we revealed a significant increase in vimentin, Slug and Snail expression with repression of E-Cadherin in MUC1-expressing cells compared with cells expressing the mutated MUC1 CT. In the cells that carried the mutated MUC1 CT, MUC1 failed to co-immunoprecipitate with ß-catenin and translocate to the nucleus, thereby blocking transcription of the genes associated with EMT and metastasis. Thus, functional tyrosines are critical in stimulating the interactions between MUC1 and ß-catenin and their nuclear translocation to initiate the process of EMT. This study signifies the oncogenic role of MUC1 CT and is the first to identify a direct role of the MUC1 in initiating EMT during pancreatic cancer. The data may have implications in future design of MUC1-targeted therapies for pancreatic cancer.

Lactobacillus and Bifidobacterium species do not secrete protease that cleaves the MUC2 mucin which organises the colon mucus.

The colon epithelium is covered by two layers of mucus built around the MUC2 mucin. An inner dense and attached mucus layer does not allow bacteria to penetrate, thus keeping the epithelial cell surface free from bacteria. An outer loose mucus layer is the habitat for the commensal bacterial microbiota. The inner mucus layer is renewed from the epithelial side and gets converted into the outer layer due to proteolytic cleavages by host proteases. We have now analysed if potential probiotic bacteria, namely Lactobacillus brevis, Lactobacillus plantarum, Lactobacillus bulgaricus and Bifidobacterium lactis, can secrete protease that cleaves the MUC2 mucin. We found that none of the potential probiotic bacteria Lactobacillus and Bifidobacterium could cleave the MUC2 core protein in the form of recombinant MUC2 N and C-termini although they secreted active proteases. This was in contrast to crude mixtures of oral and faecal bacteria that cleaved the MUC2 mucin. This observation further supports the view that these potential probiotic bacteria are of no harm to the host, as these bacteria cannot disrupt the mucin organised mucus as long as they are covered by glycans.