LPS-binding IgG arrests actively motile Salmonella Typhimurium in gastrointestinal mucus |
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| Institution: | 1. Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina – Chapel Hill, 27599, Chapel Hill, NC, USA;2. Department of Applied and Computational Mathematics, University of North Carolina – Chapel Hill, 27599, Chapel Hill, NC, USA;3. Department of Microbiology and Immunology, University of North Carolina – Chapel Hill, 27599, Chapel Hill, NC, USA;4. UNC/NCSU Joint Department of Biomedical Engineering, University of North Carolina – Chapel Hill, 27599, Chapel Hill, NC, USA;1. Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina – Chapel Hill, 27599, Chapel Hill, NC, USA;2. Department of Applied and Computational Mathematics, University of North Carolina – Chapel Hill, 27599, Chapel Hill, NC, USA;3. Department of Microbiology and Immunology, University of North Carolina – Chapel Hill, 27599, Chapel Hill, NC, USA;4. UNC/NCSU Joint Department of Biomedical Engineering, University of North Carolina – Chapel Hill, 27599, Chapel Hill, NC, USA |
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| Abstract: | The gastrointestinal (GI) mucosa is coated with a continuously secreted mucus layer that serves as the first line of defense against invading enteric bacteria. We have previously shown that antigen-specific immunoglobulin G (IgG) can immobilize viruses in both human airway and genital mucus secretions through multiple low-affinity bonds between the array of virion-bound IgG and mucins, thereby facilitating their rapid elimination from mucosal surfaces and preventing mucosal transmission. Nevertheless, it remains unclear whether weak IgG-mucin crosslinks could reinforce the mucus barrier against the permeation of bacteria driven by active flagella beating, or in predominantly MUC2 mucus gel. Here, we performed high-resolution multiple particle tracking to capture the real-time motion of hundreds of individual fluorescent Salmonella Typhimurium in fresh, undiluted GI mucus from Rag1−/− mice, and analyzed the motion using a hidden Markov model framework. In contrast to control IgG, the addition of anti-lipopolysaccharide IgG to GI mucus markedly reduced the progressive motility of Salmonella by lowering the swim speed and retaining individual bacteria in an undirected motion state. Effective crosslinking of Salmonella to mucins was dependent on Fc N-glycans. Our findings implicate IgG-mucin crosslinking as a broadly conserved function that reduces mucous penetration of both bacterial and viral pathogens. |
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