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Clinical and Diagnostic Laboratory Immunology, January 2003, p. 30-37, Vol. 10, No. 1
1071-412X/03/$08.00+0     DOI: 10.1128/CDLI.10.1.30-37.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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

Department of Environmental Health, National Public Health Institute, FIN-70701 Kuopio,¹ Department of Clinical Microbiology, University of Kuopio,² Department of Clinical Microbiology, Kuopio University Hospital,³ Department of Pathology and Forensic Medicine, University of Kuopio and Kuopio University Hospital, FIN-70211 Kuopio, Finland⁴

Received 1 May 2002/ Returned for modification 26 July 2002/ Accepted 8 September 2002

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 x 10³, 2 x 10⁵, and 2 x 10⁷ 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 inflammation- and 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 x 10⁵ 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.