Mice lacking IL-12 develop polarized Th1 cells during viral infection

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• Interleukin-12 (IL-12) is crucial for initiating T helper 1 (Th1) cytokine responses, vital for clearing intracellular pathogens.
• Previous studies established IL-12's necessity for Th1 responses in various contexts.

Purpose of the Study:

• To investigate the role of IL-12 in controlling liver damage during mouse hepatitis virus (MHV) infection.
• To determine if IL-12 is essential for generating Th1-type immune responses during viral hepatitis.

Main Methods:

• Utilized IL-12-deficient mice (lacking IL-12p40 and/or p35 genes) and interferon-gamma receptor-deficient (IFN-gammaR[-/-]) mice.
• Administered IL-12-neutralizing antibodies and performed in vivo IFN-gamma neutralization.
• Assessed Th1/Th2 cytokine profiles (IFN-gamma, IL-4) and immunoglobulin (IgG2a/IgG1, IgE) responses following MHV infection and immunization.

Main Results:

• IL-12-deficient mice effectively controlled MHV-induced liver damage, similar to wild-type mice.
• MHV-infected IFN-gammaR[-/-] mice exhibited increased susceptibility to hepatitis.
• Surprisingly, IL-12-deficient mice mounted polarized Th1 responses (high IFN-gamma, low IL-4) during MHV infection.
• Th1 responses were induced in IL-12-deficient mice upon MHV immunization, but nonviral antigen immunization led to Th2-skewed responses.

Conclusions:

• IL-12 is not essential for generating Th1 cytokine expression and immune responses during viral infections like MHV.
• Viruses may possess mechanisms to induce IFN-gamma production and Th1 responses independently of IL-12.
• This contrasts with nonviral systems where IL-12 is critical for Th1 polarization.