Blockade of CD14 increases Shigella-mediated invasion and tissue destruction

Shigella is a diarrheal pathogen that causes disease through invasion of th e large intestinal mucosa, The endotoxin of the invading bacterium may play a key role in the disease process by causing inflammation and tissue injur y during infection. Earlier studies have shown that various animal species lacking functional CD14 were protected against endotoxin-mediated shock. Ra bbits experimentally infected with Shigella were used to test the hypothesi s that blockade of endotoxin-induced cell activation with anti-CD14 mAb wou ld diminish inflammation and thus disease severity. Unexpectedly, we observ ed that the intestinal mucosa of anti-CD14-treated animals exhibited a 50-f old increase in bacterial invasion and more severe tissue injury compared w ith controls. Despite higher bacterial loads in treated animals, the number s of polymorphonuclear leukocytes that were recruited to the infection site were similar to those in controls. Furthermore, the phagocytic cells of CD 14-blocked animals produced IL-1 and TNF-alpha, Moreover, in vitro blockade of CD14 did not impede bactericidal activity. Thus, anti-CD14 treatment in terfered with host defense mechanisms involved with removal/eradication of Shigella.