Title

Antibody efficacy in murine pulmonary Cryptococcus neoformans infection: a role for nitric oxide

UMMS Affiliation

Department of Microbiology and Immunology and University of Massachusetts Medical School

Date

3-22-2002

Document Type

Article

Subjects

Animals; Antibodies, Fungal; Antigens, Fungal; Cell Movement; Cryptococcosis; Cryptococcus neoformans; Female; Injections, Intraperitoneal; Leukocyte Count; Lung; Lung Diseases, Fungal; Macrophages, Alveolar; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitrites; Phagocytosis; Polysaccharides; Survival Analysis

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

We investigated the pathogenesis of pulmonary Cryptococcus neoformans infection and passive Ab efficacy in mice deficient in inducible NO synthase (NOS2(-/-)) and the parental strain. Parental mice lived significantly longer than NOS2(-/-) mice after intratracheal infection, despite having a higher lung fungal burden. Administration of Ab reduced lung CFU in both NOS2(-/-) and parental mice, but prolonged survival and increased the inflammatory response only in parental mice. Ab administration was associated with increased serum nitrite and reduced polysaccharide levels in parental mice. Eosinophils were present in greater numbers in the lung of infected NOS2(-/-) mice than parental mice, irrespective of Ab administration. C. neoformans infection in NOS2(-/-) mice resulted in significantly higher levels of IFN-gamma, monocyte chemoattractant protein-1, and macrophage-inflammatory protein-1alpha than parental mice. Ab administration had different effects on infected NOS2(-/-) and parental mice with respect to IFN-gamma, monocoyte chemoattractant protein-1, and macrophage-inflammatory protein-1alpha levels. Ab administration increased lung levels of IFN-gamma in parental mice and reduced levels in NOS2(-/-) mice. The results indicate that NO is involved in the regulation of cytokine expression in response to cryptococcal pneumonia and is necessary for Ab efficacy against C. neoformans in mice. Our findings indicate a complex relationship between Ab efficacy against C. neoformans and cytokine expression, underscoring the interdependency of cellular and humoral defense mechanisms.

Rights and Permissions

Citation: J Immunol. 2002 Apr 1;168(7):3419-27.

Related Resources

Link to Article in PubMed

Journal Title

Journal of immunology (Baltimore, Md. : 1950)

PubMed ID

11907100