Influenza A virus and the neutrophil: a model of natural immunity

Natural immune reactions are mediated by lymphocytes, macrophages/monocytes, and neutrophils. The latter have been implicated in a variety of self-surveillance models, i.e., activity against malignant host cells, participation in wound repair, and infliction of damage in postischemic perfusion injury. Better characterized are the interactions with unopsonized pathogens through lectinophagocytosis mechanisms, where the lectin resides either on the phagocyte or on the microorganism. This review examines the infection by influenza A virus (IAV) of the human neutrophil, which results in the vigorous metabolic response of the cell to generate toxic oxygen species. This response is not necessarily characteristic of response to unopsonized particles, as the neutrophil exhibits no such activity to unopsonized zymosan or chlamydia. The virus elicits calcium mobilization from intracellular stores through a pertussis toxin-insensitive mechanism, and in its particulars the activation cascade is unique in comparison to any other characterized agonist. The putative receptor for the IAV binding protein, hemagglutinin (HA), contains the sialic acid residues; identification of specifically linked protein receptors will allow characterization of this stimulation pathway and will define the molecular biology of this activation sequence. Insight into this particular pathway may allow definition of a primitive recognition system that represents a fundamental basis for discernment of self and nonself entities.