Reactive nitrogen intermediates suppress the primary immunologic response to Listeria

Area of Science:

• Immunology
• Microbiology
• Biochemistry

Background:

• Reactive nitrogen intermediates (RNI), such as nitric oxide, show antimicrobial properties in laboratory settings.
• The in vivo role of RNI in host defense against infections remains largely undetermined.
• Listerial infections of the liver provide a model to investigate RNI's in vivo function.

Purpose of the Study:

• To elucidate the role of RNI in the resolution of primary Listeria monocytogenes infections in the liver.
• To determine if RNI contribute to host defense or influence pathogen replication in vivo.
• To investigate the impact of RNI on immune cell function during infection.

Main Methods:

• Measurement of serum and hepatic RNI levels in Listeria-infected mice.
• Assessment of RNI's direct effect on Listeria viability and hepatic cell lytic activity.
• Administration of NG-monomethyl-L-arginine (a competitive RNI inhibitor) to infected mice.
• In vitro analysis of T lymphocyte proliferation in response to antigen in the presence of the RNI inhibitor.

Main Results:

• Serum and liver RNI levels were significantly elevated in mice infected with Listeria monocytogenes.
• RNI did not directly kill Listeria or mediate hepatic cell listericidal activity.
• Elevated RNI levels correlated with increased Listeria replication in vivo.
• Administration of NG-monomethyl-L-arginine reduced Listeria burden and enhanced T lymphocyte proliferation.

Conclusions:

• Contrary to in vitro findings, elevated RNI production during primary listerial infection promotes pathogen replication in vivo.
• RNI appear to suppress host immune defenses by inhibiting T lymphocyte proliferation.
• Inhibiting RNI may represent a therapeutic strategy to bolster host defense against Listeria infections.