Antibody against Microbial Neuraminidases Recognizes Human Sialidase 3 (NEU3): the Neuraminidase/Sialidase Superfamily Revisited

ABSTRACTNeuraminidases (NAs) are critical virulence factors for several microbial pathogens. With a highly conserved catalytic domain, a microbial NA “superfamily” has been proposed. We previously reported that murine polymorphonuclear leukocyte (PMN) sialidase activity was important in leukocyte trafficking to inflamed sites and that antibodies to Clostridium perfringensNA recognized a cell surface molecule(s), presumed to be a sialidase of eukaryotic origin on interleukin-8-stimulated human and murine PMNs. These antibodies also inhibited cell sialidase activity both in vitroand, in the latter instance, in vivo. We therefore hypothesized that mammalian sialidases share structural homology and epitopes with microbial NAs. We now report that antibodies to one of the isoforms of C. perfringensNA, as well as anti-influenza virus NA serum, recognize human NEU3 but not NEU1 and that antibodies to C. perfringensNA inhibit NEU3 enzymatic activity. We conclude that the previously described microbial NA superfamily extends to human sialidases. Strategies designed to therapeutically inhibit microbial NA may need to consider potential compromising effects on human sialidases, particularly those expressed in cells of the immune system.IMPORTANCEWe previously reported that sialidase activity of human neutrophils plays a critical role in the host inflammatory response. Since the catalytic domains of microbial neuraminidases are highly conserved, we hypothesized that antibodies against Clostridium perfringensneuraminidase might inhibit mammalian sialidase activity. Before the recognition of four mammalian sialidase (Neu) isoforms, we demonstrated that anti-C. perfringensneuraminidase antibodies inhibited human and murine sialidase activity in vivoand in vitro. We now show that the antibodies to microbial neuraminidase (C. perfringensand influenza virus) recognize human NEU3, which is important for neural development and cell signaling. Since many microbes that infect mucosal surfaces express neuraminidase, it is possible that the use of sialidase inhibitors (e.g., zanamivir), might also compromise human sialidase activity critical to the human immune response. Alternatively, sialidase inhibitors may prove useful in the treatment of hyperinflammatory conditions.