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Fas (CD95)-dependent cell-mediated immunity to Listeria monocytogenes
E R Jensen1, A A Glass, W R Clark
1Departments of Microbiology and Immunology, University of California at Los Angeles, Los Angeles, California 90095, USA.
Infection and Immunity
|August 26, 1998
Summary
Host defenses against Listeria monocytogenes involve perforin and CD95 (Fas) pathways. Both pathways are crucial for clearing the infection and developing immunity, with Fas-dependent cytotoxic T lymphocytes (CTL) playing a key role in eliminating infected liver cells.
Area of Science:
- Immunology
- Infectious Diseases
- Cell Biology
Background:
- Cell-mediated cytotoxicity is essential for host defense.
- Two primary pathways, perforin-mediated and CD95 (Fas)-dependent, mediate this cytotoxicity.
- The intracellular bacterium Listeria monocytogenes serves as a model pathogen to study these immune mechanisms.
Purpose of the Study:
- To investigate the distinct and complementary roles of perforin and Fas pathways in controlling Listeria monocytogenes infection.
- To elucidate the contribution of these pathways to both primary and secondary immune responses.
- To determine the mechanism of cytotoxic T lymphocyte (CTL) mediated lysis of infected hepatocytes.
Main Methods:
- Generation of mice lacking both perforin and Fas (P0L0) for comparative studies.
- Assessment of bacterial loads in spleen and liver during primary and secondary listeriosis in wild-type (WT), Fas-deficient (L0), and perforin knockout (P0) mice.
- In vitro analysis of cytotoxic T lymphocyte (CTL) activity against L. monocytogenes-infected hepatocytes.
Main Results:
- Mice lacking perforin (P0) showed impaired splenic clearance, while Fas-deficient (L0) mice had increased liver bacterial titers.
- Mice lacking both pathways (P0L0) exhibited significantly higher bacterial loads and delayed clearance in both spleen and liver.
- P0L0 mice demonstrated reduced resistance to secondary listeriosis.
- In vitro, Fas-dependent CTLs were critical for lysing infected hepatocytes, independent of perforin.
Conclusions:
- Both perforin and Fas pathways play complementary roles in host defense against Listeria monocytogenes.
- Fas-mediated cytotoxicity by CD8(+) CTLs is essential for eliminating infected hepatocytes.
- Understanding these pathways provides insights into immune strategies against intracellular bacterial infections.