Human PMNs exhibit greater phagocytosis, NETosis, and enhanced migration towards nontypeable Haemophilus influenzae newly released from biofilms Wilbanks et al.

Biofilms exhibit diverse evasion mechanisms, thus releasing bacteria from biofilm residence affords both antibiotics and immune effectors greater access. A monoclonal antibody against an essential biofilm matrix protein induces rapid biofilm collapse with release of bacteria into a highly vulnerable phenotype. Newly released (‘NRel’) bacteria are significantly more sensitive to antibiotic-, PMN-, or antimicrobial peptide-mediated killing in vitro, and are rapidly eradicated in four animal models without antibiotic treatment, highlighting the role of innate immune effectors. Here, we characterize PMN-mediated activity against three clinical isolates of nontypeable Haemophilus influenzae NRel. Indeed, NTHI was most sensitive in the NRel state to both PMN-mediated phagocytosis and NETosis elimination. Moreover, PMNs incubated with NTHI NRel released significantly more IL-8 to recruit additional PMNs. These data provide the mechanism and treatment regimen to facilitate host mediated biofilm eradication in our pre-clinical models where biofilm bacteria were induced into the highly vulnerable NRel state.