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Genetic control of macrophage susceptibility to infection by Legionella pneumophila
Y Yamamoto1, T W Klein, H Friedman
1Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, Tampa 33612.
Abstract:
Legionella pneumophila readily grows in cultures of thioglycollate (TGC)-induced macrophages (MPs) from A/J mice, but not in MPs from BALB/c mice or other mouse strains. In the present study, the growth of Legionella pneumophilia in MPs from A/J and BALB/c mice, as well as hybrids of the two strains and back-crossed mice, was investigated to determine whether the permissiveness of growth of these bacteria was due to an inherited trait of the MPs. The MPs from all A/J mice supported the growth of Legionella, regardless of whether they were obtained from TGC or casein injected donors, but the cells from the mice given TGC supported growth of L. pneumophila much better than cells from mice injected with casein. Furthermore, MPs obtained from all BALB/c mice treated with either TGC or casein were nonpermissive for the growth of L. pneumophila. MPs from approximately 46% of the back-crossed ACF1 to A/J mice were permissive for L. pneumophila growth, while MPs from all ACF1 to back-crossed BALB/c mice were found to be nonpermissive. MPs from approximately 19% of ACF2 mice were permissive for L. pneumophila. Killing activities of MPs using temperature sensitive mutants of Salmonella typhimurium were variable and did not correlate with permissiveness or nonpermissiveness for growth of L. pneumophila.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
The susceptibility of macrophages to Legionella pneumophila infection is an inherited trait. Macrophages from A/J mice support bacterial growth, while those from BALB/c mice do not, indicating a genetic basis for permissiveness.
Area of Science:
- Immunology
- Genetics
- Microbiology
Background:
- Legionella pneumophila (L. pneumophila) infection outcome varies significantly between mouse strains.
- A/J mouse macrophages (MPs) readily support L. pneumophila growth, unlike BALB/c mouse MPs.
Purpose of the Study:
- To investigate the genetic basis of macrophage permissiveness to L. pneumophila growth.
- To determine if macrophage permissiveness is an inherited trait.
Main Methods:
- Culturing L. pneumophila in macrophages from A/J, BALB/c, and their hybrid/back-crossed offspring.
- Inducing macrophages using thioglycollate (TGC) or casein.
- Assessing macrophage killing activity using Salmonella typhimurium mutants.
Main Results:
- All A/J macrophages supported L. pneumophila growth, with TGC-induced cells being more permissive than casein-induced.
- BALB/c macrophages were nonpermissive regardless of induction method.
- Back-crossed mice showed varying permissiveness (e.g., ~46% permissive in ACF1 to A/J), suggesting genetic inheritance.
- Macrophage killing activity did not correlate with L. pneumophila permissiveness.
Conclusions:
- Macrophage permissiveness to L. pneumophila is an inherited trait.
- Genetic factors in macrophages dictate susceptibility or resistance to L. pneumophila infection.