Pulmonary Exposure to 1 → 3-β-Glucan Alters Adaptive Immune Responses in Rats

Abstract

1 → 3-β-Glucans have been associated with increased pulmonary inflammation in fungal-related indoor air problems. Epidemiological studies have shown a correlation between increases in T-cell proliferation and decreases in CD4+/CD8+ ratio after exposure to fungi. The objective of the present investigation was to determine the mechanisms by which 1 → 3-β-glucans affect immune responses using an animal model. Rats received a single dose of zymosan A (2.5 mg/kg body weight) via intratracheal instillation (IT) and were euthanized on days 1, 4, 6, 8, and 10 post IT. Bronchoalveolar lavage was performed at each time point post-IT. Inflammation and lung injury were assessed by measuring neutrophil infiltration into bronchoalveolar lavage fluid (BALF) and by measuring albumin and lactate dehydrogenase levels in BALF, respectively. Alveolar macrophage activation was determined by chemiluminescence. Immune response was characterized via immunophenotyping of bronchoalveolar lavage cells and lymphocytes isolated from the lung-associated lymph nodes. Upon challenge with zymosan, rats exhibited increased inflammation and injury at early time points (days 1 and 4) post IT exposure. Although elevations in neutrophil infiltration and chemiluminescence had returned to control levels on day 4, lymphocytes recovered from lung-associated lymph nodes continued to proliferate and reached a maximum on day 6. The CD4+/CD8+ T cell ratio from lymph nodes was lower in zymosan-treated rats than in control rats. Zymosan treatment increased tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and IL-12p70 secretion in BALF on day 1. In summary, rats exposed to zymosan had an increase in acute inflammation, and the altered lymphocyte profiles were consistent with the findings of epidemiology studies.