Systemic Immunoresponses in Mice after Repeated Exposure of Lungs to Spores of Streptomyces californicus

Abstract

Microbial growth in moisture-damaged buildings is associated with respiratory and other symptoms in the occupants. Streptomyces spp. are frequently isolated from such buildings. In the present study, we evaluated the responses of mice after repeated exposure to spores of Streptomyces californicus. Mice were exposed via intratracheal instillation to six doses (at 7-day intervals) of the spores of S. californicus, originally isolated from the indoor air of a moisture-damaged building, at three dose levels (2 ؋ 10 3 , 2 ؋ 10 5 , and 2 ؋ 10 7 spores). Inflammation and toxicity, including changes in cell populations in the lungs, lymph nodes, and spleen, were evaluated 24 h after the last dosage. The exposure provoked a dose-dependent inflammatory cell response, as detected by the intense recruitment of neutrophils, but the numbers of macrophages and lymphocytes in the airways also increased. The cellular responses corresponded to the dose-dependent increases in inflammationand cytotoxicity-associated biochemical markers (i.e., levels of albumin, total protein, and lactate dehydrogenase) in bronchoalveolar lavage fluid. The spore exposure increased the number of both activated and nonactivated T lymphocytes. Also, the amounts of CD3 ؊ CD4 ؊ and unconventional CD3 ؊ CD4 ؉ lymphocytes in the lung tissue were augmented. Interestingly, the spore exposure decreased cells in the spleen. This effect was strongest at the dose of 2 ؋ 10 5 spores. These results indicate that the spores of S. californicus are capable of provoking both immunostimulation in lungs (inflammation) and systemic immunotoxicity, especially in the spleen. The immunotoxic effect resembled that caused by chemotherapeutic agents, originally isolated from Streptomyces spp. Thus, S. californicus must be considered a microbial species with potential to cause systemic adverse health effects in occupants of moisture-damaged buildings.Microbial growth subsequent to moisture damage in buildings has been connected to increased adverse respiratory and other harmful health effects (7,32,33,37,38,44). Increased numbers of microbial spores are present in the indoor air of moisture-damaged buildings (15,16,27). Moreover, several of the microbial species that are frequently detected in moisturedamaged buildings are rarely observed in reference buildings (34). The spores are inhaled deeply into the lungs due to their relatively small particle size (23). Since the spores may also deliver nonvolatile microbial toxins into the lungs (36), they presumably play a role in provoking adverse health effects.Streptomyces californicus is a sporulating gram-positive bacterium that is used as a moisture indicator and that is frequently isolated from the indoor air of moisture-damaged buildings (27,34). Streptomycetes have the genetic capability to produce many bioactive secondary metabolites, such as antibiotics, immunosuppressive agents, antitumor substances, and inhibitors of Ca 2ϩ -and calmodulin-dependent cyclic nucleotide phosphodiesterases, which are important enzymes involved ...

Analysis of Actinobacteria from mould-colonized water damaged building material

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Bioaerosols and sick building syndrome: particles, inflammation, and allergy

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