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Infection and Immunity, August 2006, p. 4549-4556, Vol. 74, No. 8
0019-9567/06/$08.00+0     doi:10.1128/IAI.00243-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Effect of Lung Surfactant Collectins on Bronchoalveolar Macrophage Interaction with Blastomyces dermatitidis: Inhibition of Tumor Necrosis Factor Alpha Production by Surfactant Protein D

Division of Infectious Diseases, Department of Medicine, Santa Clara Valley Medical Center, and California Institute for Medical Research, San Jose, California,¹ Division of Pulmonary Biology and Critical Care Medicine, Children's Hospital Medical Center, Cincinnati, Ohio,² Veterans Affairs Medical Center, Cincinnati, Ohio,³ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri,⁴ Department of Medicine, Stanford University School of Medicine, Stanford, California⁵

Received 14 February 2006/ Returned for modification 18 March 2006/ Accepted 7 May 2006

Alveolar surfactant modulates the antimicrobial function of bronchoalveolar macrophages (BAM). Little is known about the effect of surfactant-associated proteins in bronchoalveolar lavage fluid (BALF) on the interaction of BAM and Blastomyces dermatitidis. We investigated BALF enhancement or inhibition of TNF- production by BAM stimulated by B. dermatitidis. BAM from CD-1 mice were stimulated with B. dermatitidis without or with normal BALF, surfactant protein A-deficient (SP-A^–/–) or surfactant protein D-deficient (SP-D^–/–) BALF, or a mixture of SP-A^–/– and SP-D^–/– BALF. An enzyme-linked immunosorbent assay was used to measure tumor necrosis factor alpha (TNF-) in culture supernatants. BALFs were standardized in protein concentration. BAM plus B. dermatitidis (BAM-B. dermatitidis) TNF- production was inhibited 47% by BALF or SP-A^–/– BALF (at 290 or 580 µg of protein/ml, P < 0.05 to 0.01); in contrast, SP-D^–/– BALF did not significantly inhibit TNF- production. If SP-A^–/– BALF was mixed in equal amounts with SP-D^–/– BALF, TNF- production by BAM-B. dermatitidis was inhibited (P < 0.01). Finally, pure SP-D added to SP-D^–/– BALF inhibited TNF- production by BAM-B. dermatitidis (P < 0.01). B. dermatitidis incubated with BALF and washed, plus BAM, stimulated 63% less production of TNF- than did unwashed B. dermatitidis (P < 0.05). SP-D was detected by anti-SP-D antibody on BALF-treated unwashed B. dermatitidis in an immunofluorescence assay (IFA). The BALF depleted by a coating of B. dermatitidis lost the ability to inhibit TNF- production (P < 0.05). 1,3-ß-Glucan was a good stimulator of BAM for TNF- production and was detected on B. dermatitidis by IFA. ß-Glucan incubated with BALF inhibited the binding of SP-D in BALF to B. dermatitidis as demonstrated by IFA. Our data suggest that SP-D in BALF binds ß-glucan on B. dermatitidis, blocking BAM access to ß-glucan, thereby inhibiting TNF- production. Thus, whereas BALF constituents commonly mediate antimicrobial activity, B. dermatitidis may utilize BALF constituents, such as SP-D, to blunt the host defensive reaction; this effect could reduce inflammation and tissue destruction but could also promote disease.

Editor: A. Casadevall

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