Outer membrane proteins (OMP) are expressed in Gram-negative bacterial cell wall. OmpA from Klebsiella pneumoniae (KpOmpA) has been shown to bind and to activate selectively antigen presenting cells (APCs), eliciting protective CTL responses. In this study, we investigated whether OmpX, another member of the OMP family and structurally related to OmpA, exhibits the same immune properties. Using recombinant OmpX from Escherichia coli (EcOmpX), we report that EcOmpX binds to and is internalized by human APCs. However, EcOmpX does not activate APCs. EcOmpX acts as an efficient carrier protein as it induces a potent and Th1/Th2 mixed anti-TNP humoral response. However, adjuvant is required to generate a protective anti-tumoral immune response in mice injected with a tumor model antigen coupled to EcOmpX. Collectively, these data show that EcOmpX is recognized by innate cells but does not activate them, suggesting that EcOmpX does not provide a signal danger to APCs. In conclusion, this study provides information on the molecular mechanisms involved in the recognition and activation of innate cells by bacterial outer membrane proteins.