A new tool to quantify receptor recruitment to cell contact sites during host-pathogen interaction

• Published in: PLoS computational biology Vol. 10; no. 5; p. e1003639
• Main Authors: Graus, Matthew S, Pehlke, Carolyn, Wester, Michael J, Davidson, Lisa B, Steinberg, Stanly L, Neumann, Aaron K
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-05-2014; Public Library of Science (PLoS)
• Subjects: Biology and Life Sciences; Biomedical research; Cell Communication - immunology; Cell interaction; Cell research; Cells, Cultured; Computer Simulation; Dendritic Cells - immunology; Dendritic Cells - microbiology; Drug therapy; Fungal infections; Fungi; Fungi - immunology; Health aspects; Host-parasite relationships; Host-Pathogen Interactions - immunology; Humans; Methods; Microbiological research; Models, Immunological; Mortality; Nosocomial infections; Pathogenic microorganisms; Physical Sciences; Receptors, Cell Surface - immunology; Yeast
• ISSN: 1553-7358; 1553-734X; 1553-7358
• DOI: 10.1371/journal.pcbi.1003639

To understand the process of innate immune fungal recognition, we developed computational tools for the rigorous quantification and comparison of receptor recruitment and distribution at cell-cell contact sites. We used these tools to quantify pattern recognition receptor spatiotemporal distributions in contacts between primary human dendritic cells and the fungal pathogens C. albicans, C. parapsilosis and the environmental yeast S. cerevisiae, imaged using 3D multichannel laser scanning confocal microscopy. The detailed quantitative analysis of contact sites shows that, despite considerable biochemical similarity in the composition and structure of these species' cell walls, the receptor spatiotemporal distribution in host-microbe contact sites varies significantly between these yeasts. Our findings suggest a model where innate immune cells discriminate fungal microorganisms based on differential mobilization and coordination of receptor networks. Our analysis methods are also broadly applicable to a range of cell-cell interactions central to many biological problems.