A critical role of natural immunoglobulin M in immediate defense against systemic bacterial infection

To evaluate the role of natural immunoglobulin (Ig)M in the immediate respo nse against microbial infection, wt tested mutant mice that are deficient i n secreted (s)IgM in an acute peritonitis model induced. by cecal ligation and puncture (CLP). 20% of wild-type mice died within 32 h of CLP, whereas 70% of sIgM-deficient mice died within the same time period, The increased susceptibility was associated with a reduced level of tumor necrosis factor (TNF)-alpha, a decreased neutrophil recruitment and art increased bacteria l load in the peritoneum, and elevated levels of endotoxin and proinflammat ory cytokines in the circulation. Resistance to CLP by sIgM-deficient mice was restored by reconstitution with polyclonal IgM from normal mouse serum. Reconstitution with a monoclonal IgM specific to phosphatidylcholine, a co nserved cell membrane component, has a modest effect but a monoclonal IgM s pecific to phosphocholine is nut protective. These findings demonstrate a c ritical role of natural IgM in the immediate defense against severe bacteri al infection.