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Contribution of rabbit leukocyte defensins to the host response in experimental syphilis
L A Borenstein1, T Ganz, S Sell
1Department of Microbiology and Immunology, University of California, Los Angeles 90024.
Abstract:
In the companion paper (L. A. Borenstein, M. E. Selsted, R. I. Lehrer, and J. N. Miller, Infect. Immun. 59:1359-1367, 1991), we report that rabbit alveolar macrophage and neutrophil derived defensins possess antimicrobial activity against Treponema pallidum subsp. pallidum, the etiologic agent of syphilis. In this study, antisera specific for NP-1 and NP-2 (defensins present in certain macrophages and polymorphonuclear leukocytes) and NP-5 (a defensin produced only in neutrophils) were used to detect these peptides by immunoperoxidase staining in testicular lesions from infected rabbits. Profound amounts of cell-free and cell-associated defensins were detected in the tunica albuginea and interstitial spaces during the first 24 h of infection. The presence of defensins was transient and almost undetectable by day 4. Interstitial defensins were detected again at day 10 and increased through day 16, at which time lesion healing was evident by hematoxylin and eosin staining. The appearance and increase in detectable defensins between days 10 and 16 of infection correlated with a reduction in numbers and disappearance of T. pallidum, as demonstrated by using silver staining. The extent and pattern of immunostaining for NP-1 and NP-2 corresponded with immunostaining for NP-5 and identified neutrophils as the cellular source of the defensins. These findings indicate that defensins may contribute to the control of local T. pallidum infection and suggest a role for acute inflammatory processes in the resolution of early experimental syphilis.
Insights
Defensins, antimicrobial peptides found in neutrophils and macrophages, were detected in rabbit syphilis lesions. Their transient appearance correlated with the clearance of Treponema pallidum, suggesting a role in controlling infection.
Area of Science:
- Immunology
- Microbiology
- Pathology
Background:
- Defensins are antimicrobial peptides with known activity against Treponema pallidum.
- Rabbit alveolar macrophages and neutrophils produce defensins.
Purpose of the Study:
- To investigate the presence and localization of defensins in experimental syphilis lesions.
- To determine the cellular source of defensins during infection.
- To correlate defensin presence with Treponema pallidum load and lesion healing.
Main Methods:
- Immunoperoxidase staining using antisera specific for NP-1, NP-2, and NP-5 defensins.
- Detection of defensins in testicular lesions of infected rabbits at various time points.
- Silver staining to quantify Treponema pallidum.
- Hematoxylin and eosin staining for lesion assessment.
Main Results:
- Defensins (NP-1, NP-2, NP-5) were detected in testicular lesions, primarily associated with neutrophils.
- Defensin levels peaked within the first 24 hours, decreased by day 4, and reappeared by day 10, increasing through day 16.
- Increased defensin levels correlated with a reduction in Treponema pallidum and signs of lesion healing.
Conclusions:
- Neutrophil-derived defensins are present in experimental syphilis lesions.
- Defensins may play a role in the host's control of local Treponema pallidum infection.
- Acute inflammatory processes, involving defensins, likely contribute to the resolution of early syphilis.