Disclosed are immunomodulatory polypeptides that behave as weak TLR2 and TLR4 agonists and as potent competitive antagonists of natural pathogenic ligands for human and murine TLR2 and TLR4, that identify a subset of neutrophils in human peripheral blood leukocytes, and that elicit an unusual induced cytokine profile. Also disclosed are compositions comprising such polypeptides, compositions comprising antibodies that specifically bind to such polypeptides, and methods of using the same, including for treating sepsis or reducing the severity or likelihood of occurrence of sepsis, in cancer treatment, in the treatment of autoimmune diseases, in organ transplantation and for reducing graft rejection, for promoting fertility, and for identifying a neutrophil subset and/or other cellular subset including by flow cytometry. Pharmaceutical compositions and kits, and treatment methods are also disclosed.