Role of Escherichia coli endopeptidases and dd-carboxypeptidases in infection and regulation of innate immune response

• Published in: Microbes and infection Vol. 21; no. 10; pp. 464 - 474
• Main Authors: Mallick, Sathi, Das, Joyjyoti, Verma, Jyoti, Mathew, Samatha, Maiti, Tapas K., Ghosh, Anindya S.
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01-12-2019
• Subjects: Animals; Carboxypeptidases - genetics; Carboxypeptidases - immunology; Cytokines - metabolism; dd-Carboxypeptidase; Endopeptidase; Endopeptidases - genetics; Endopeptidases - immunology; Escherichia coli; Escherichia coli - enzymology; Escherichia coli - growth & development; Escherichia coli - pathogenicity; Escherichia coli Infections - immunology; Escherichia coli Infections - metabolism; Escherichia coli Proteins - genetics; Escherichia coli Proteins - immunology; Immunity, Innate; Infection; Macrophages; Macrophages - immunology; Macrophages - metabolism; Macrophages - microbiology; Mice; Microbial Viability; Nitric Oxide - metabolism; Penicillin-binding proteins; Penicillin-Binding Proteins - genetics; Penicillin-Binding Proteins - immunology; RAW 264.7 Cells; Reactive Oxygen Species - metabolism; Receptors, Cell Surface - metabolism; Sequence Deletion; Penicillin-binding proteins; Infection; dd-Carboxypeptidase; Macrophages; Endopeptidase; Escherichia coli
• ISSN: 1286-4579; 1769-714X
• DOI: 10.1016/j.micinf.2019.04.007

The low-molecular-mass penicillin-binding proteins, involved in peptidoglycan recycling can also produce peptidoglycan fragments capable of activating an innate immune response in host. To investigate how these proteins in Enterobacteriaceae play a role to elicit/evade innate immune responses during infections, we deleted certain endopeptidases and dd-carboxypeptidases from Escherichia coli CS109 and studied the viability of these mutants in macrophages. The ability of infected macrophages to exert oxidative killing, express surface activation markers TLR2, MHC class II and release TNFα, were assessed. Immune responses were elevated in macrophages infected with dd-carboxypeptidase mutants but reduced for endopeptidase mutants. However, the NFκB, iNOS, and TLR2 transcripts remained elevated in macrophages infected with both mutant types. Overall, we have shown, under normal conditions endopeptidases have a tendency to elicit the immune response but their effect is suppressed by the presence of dd-carboxypeptidases. Conversely, DD-carboxypeptidases, normally, tend to reduce immune responses, as their deletions enhanced the same in macrophages. Therefore, we conclude that the roles of endopeptidases and dd-carboxypeptidases are possibly counter-active in wild-type cells where either class of enzymes suppresses each other's immunogenic properties rendering overall maintenance of low immunogenicity that helps E. coli in evading the host immune responses.