Kl. Hartshorn et al., HUMAN MANNOSE-BINDING PROTEIN FUNCTIONS AS AN OPSONIN FOR INFLUENZA-AVIRUSES, The Journal of clinical investigation, 91(4), 1993, pp. 1414-1420
Influenza A viruses (IAVs) cause substantial morbidity and mortality i
n yearly epidemics, which result from the ability of the virus to alte
r the antigenicity of its envelope proteins. Despite the rapid replica
tion of this virus and its ability to infect a wide variety of cell ty
pes, viremia is rare and the infection is generally limited to the upp
er respiratory tract. The preimmune host defense response against IAV
is generally, therefore, successful. We have previously provided (and
summarized) evidence that neutrophils contribute to defense against IA
V, although neutrophil dysfunction and local tissue damage may be less
salutory byproducts of this response. Here we provide evidence that t
he serum lectin mannose-binding protein directly inhibits hemagglutini
n activity and infectivity of several strains of IAV. In addition mann
ose-binding protein acts as an opsonin, enhancing neutrophil reactivit
y against IAV. Opsonization of IAV by mannose-binding protein also pro
tects the neutrophil from IAV-induced dysfunction. These effects are o
bserved with physiologically relevant concentrations of mannose-bindin
g protein. Two different allelic forms of recombinant mannose-binding
protein are found to have similar effects. We believe, on the basis of
these data, that mannose-binding protein alone and in conjunction wit
h phagocytic cells is an important constituent of natural immunity (i.
e., preimmune defense) against IAV.