PREEXPOSURE TO REPEATED LOW DOSES OF ZYMOSAN INCREASES THE SUSCEPTIBILITY TO PULMONARY INFECTION IN RATS

Abstract

Chronic exposure to low levels of mold has been reported to increase susceptibility to respiratory infections. In the current study, the authors investigate the lungs' ability to clear an infection after repeated low-dose zymosan exposure. Exposure was conducted at a zymosan dose of 0.6 mg/kg body weight (bw) of rat, for a total of 4 doses, via intratracheal instillation during a 2 week period. Treated animals were allowed to recover for 1 week before pulmonary inoculation with Listeria monocytogenes. Bacterial clearance was determined by measuring colony-forming units cultured from the left lungs on days 3, 5, and 7 post bacteria infection. Bronchoalveolar lavage (BAL) was performed on the right lungs to recover phagocytes and BAL fluid to measure lung injury and the inflammatory cytokines. In contrast to the authors' previously published study that showed a single high dose (2.5 mg/kg bw) of zymosan prior to infection accelerated bacteria clearance, the repeated low-dose zymosan suppressed bacteria clearance from the lungs early after infection and induced higher lung injury and inflammation compared to control. The innate immune response was down-regulated and a Th2 immune response was preferentially induced rather than a Th1 response, the latter being more effective toward the resolution of a L. monocytogenes infection.

Keywords:

• 1 →3-β-glucans
• fungal infections
• Listeria monocytogenes
• lung inflammation
• pulmonary clearance

Notes

¹FITC, fluorescein isothiocyanate; PE, phycoerythrin; APC, allophycocyanin.