Effect of a local immune reaction on peripheral blood polymorphonuclear neutrophil microbicidal function: Studies with fungal targets

Abstract

Peripheral blood polymorphonuclear neutrophils (PMN) from mice immunized with Blastomyces dermatitidis and then stimulated locally (intraperitoneally, ip) with B. dermatitidis antigen had enhanced killing of B. dermatitidis in vitro (54.4 ± 19.4% of inoculum) compared to nonimmune mice (32.7 ± 8.7%; P < 0.02), nonimmune mice given antigen ip (30.6 ± 14.0%; P < 0.05), or immune mice not given antigen ip (15.4 ± 9.9%; P < 0.01). Peripheral blood PMN from all four groups had marked killing ability against Candida albicans (91.8–99.3% of inoculum). That the killing of B. dermatitidis was due to PMNs was demonstrated by lack of killing by isolated peripheral blood mononuclear cells from all four groups. A local immune reaction can result in enhancement of PMN fungicidal activity, and this is reflected even in peripheral blood PMN. We hypothesize this is an important component of normal host defenses against fungal infection, and likely other microbial infections. Enhancement of PMN microbicidal function by the soluble mediators presumed to be responsible for the effects observed may be an approach to immunomodulating therapy or prophylaxis of infection.