Single Pre-Exposure to a High Dose of Zymosan Enhances Lung Defense Mechanisms and Accelerates the Pulmonary Clearance of a Bacterial Pathogen in Rats

Abstract

The present study examines the effects of pre-exposure to zymosan (a 1 --> 3-beta-glucan from baker yeast) on lung defense against bacterial infection. Rats received a single dose of zymosan A (0.6, 1.2, or 2.5 mg/kg body weight [bw]) or vehicle control (saline) via intratracheal instillation 3 days prior to intratracheal inoculation with 5 x 10(5) Listeria monocytogenes. Left lungs were homogenized and cultured to assess bacterial clearance, and bronchoalveolar lavage was performed on the right lungs to monitor lung inflammation and injury. Prior to bacterial infection, zymosan exposure resulted in elevated inflammation and oxidant production in the lungs. Zymosan treatment followed by infection led to an accelerated pulmonary clearance of bacteria when compared to the saline control group in a dose-dependent fashion. In addition, lower levels of injury and inflammation were associated with the enhanced bacteria clearance observed in zymosan-infected rats. Our findings suggest that zymosan exposure may enhance the lung immune response by activating alveolar macrophages prior to infection, and stimulating T cells involved in the adaptive immune response early after infection, thus resulting in a heightened pulmonary immune response.

Polysaccharides purified from the submerged culture of Ganoderma formosanum stimulate macrophage activation and protect mice against Listeria monocytogenes infection

“…The observed stimulatory effects on macrophages in vitro most likely also occurred in vivo since PS-F2 challenge resulted in a marked influx of neutrophils and monocytes and protected mice from a subsequent infection of L. monocytogenes. b-Glucan exerts anti-infective effects on microorganisms, such as Leishmania donovani, influenza virus (Irinoda et al 1992), and L. monocytogenes (Young et al 2008). In these and our studies, animals administered with fungal polysaccharides exhibit enhanced microbial killing, which is mostly mediated by monocytes/macrophages and neutrophils.…”

Mold exposure and respiratory health in damp indoor environments

“…More research is needed to substantiate these theories. In a rat model, a one-time high dose of fungal cell wall (1→3)-β-D-glucan enhanced the lung immune response by activating alveolar macrophages prior to infection, and stimulating T cells involved in the adaptive immune response early after infection with the bacteria Listeria monocytogenes (141). Yet in a following study, a similar total dose of zymosan divided into four smaller repeated doses suppressed the host defense against Listeria monocytogenes by downregulating the innate response (142).…”

Adjuvant effect of zymosan after pulmonary treatment in a mouse ovalbumin allergy model

“…Among the total polysaccharides, 50-57% are glucans and 16-22% are mannan. Zymosan has been shown to induce lung inflammation [9], alter adaptive immune response [10], and affect lung clearance of a bacterial pathogen [11,12] after pulmonary treatment when evaluated using an animal model. In a comparison of the pulmonary inflammatory potential of different components of yeast and fungal cell walls, 1→3-β-glucan was the most potent inflammatory agent tested, and zymosan, the crude B-glucan preparation, had a greater inflammatory activity than a partially purified particulate 1→3-β-glucan [13].…”