Significance Our previous work has shown that bacterial-induced activation of neutrophil granulocytes after allogeneic hematopoietic cell transplantation promotes acute graft-versus-host disease (GVHD). In patients, depleting neutrophils is not possible because they mediate protection from invading bacteria and antibiotic treatment needed to reduce bacteria-induced neutrophil activation affects protective intestinal microbiota. Here, we describe that active and passive immunization against the conserved microbial surface polysaccharide poly- N -acetylglucosamine leads to killing of invading bacteria, which reduces the uncontrolled neutrophil activation, and thereby opens a new avenue to interfere with acute GVHD without affecting commensal intestinal microbial diversity.