muramidase and Enterocolitis

Mucosal immunity protects a host from intestinal inflammation and infection and is profoundly influenced by symbiotic bacteria. Here we report that in mice symbiotic bacteria directed selective cargo sorting in Paneth cells to promote symbiosis through Nod2, a cytosolic bacterial sensor, and the multifunctional protein kinase LRRK2, both encoded by inflammatory bowel disease (IBD)-associated genes. Commensals recruited Nod2 onto lysozyme-containing dense core vesicles (DCVs), which was required for DCV localization of LRRK2 and a small GTPase, Rab2a. Deficiency of Nod2, LRRK2 or Rab2a or depletion of commensals resulted in lysosomal degradation of lysozyme. Thus, commensal bacteria and host factors orchestrate the lysozyme-sorting process to protect the host from enteric infection, implicating Paneth cell dysfunction in IBD pathogenesis.

Topics: Animals; Enterocolitis; Immunity, Mucosal; Inflammatory Bowel Diseases; Intestines; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Listeriosis; Lysosomes; Mice; Mice, Knockout; Muramidase; Nod2 Signaling Adaptor Protein; Paneth Cells; Protein Serine-Threonine Kinases; rab GTP-Binding Proteins; Secretory Vesicles; Symbiosis

Two comparable groups made up of 15 neonates with intestinal infections induced by opportunistic bacteria were under observation. The children of group 1 received lysozyme in a dose of 25 mg/kg a day for 7-10 days together with conventional therapy Lysozyme appeared to promote the reduction of the disease duration and the rise of the phagocytic reserves of peripheral blood neutrophils in the children examined.

Topics: Adjuvants, Immunologic; Bacterial Infections; Enterocolitis; Humans; Immune Tolerance; Infant, Newborn; Muramidase; Phagocytosis; T-Lymphocytes