Differential regulation of Ia expression and antigen presentation by listeriolysin-producing versus non-producing strains of Listeria monocytogenes

Listeria monocytogenes is an intracellular bacterial pathogen. A single gene product, listeriolysin (LLO), is critical for the induction of protective immunity. We now show that listeria that produce functional LLO augment Ia expression by macrophages and are better presented to a Th1, CD4⁺ anti-listeria T cell line. We used two genetically engineered strains of listeria which differed only in their ability (Ly⁺) or inability (Ly^-) to produce functional LLO. Ia-negative murine macrophages ingested either Ly⁺ or Ly^-, and then were stimulated by interferon-γ (IFN-γ). Increasing numbers of live Ly⁺, but not Ly^-, augmented IFN-γ-induced Ia expression. Ly⁺ by itself did not induce Ia expression. Heat-killed Ly⁺ and Ly^- did not augment IFN-γ-induced Ia expression. The abundance of Ia on the macrophage cell surface is one major determinant of antigen presentation to CD4⁺ T cells. Consistent with their ability to augment Ia expression, Ly⁺ were better presented than Ly^- to a CD4⁺, Th1, anti-listeria T cell line. When macrophages and T cells were from different inbred mouse strains, antigen presentation required identity at the Class II region of the MHC gene complex. This indicated that antigen presentation occurred via Ia molecules. The increased ability of macrophages to present Ly⁺ is a product of the macrophage-listeria interaction, not a property of the T cell line 86. If Ia- negative macrophages ingested Listeria and were then stimulated by IFN-γ, Ly⁺ was presented more efficiently than Ly^-. On the other hand, if Ia- positive macrophages ingested Listeria, then Ly⁺ and Ly^- were presented equally web to T cells. Altogether our data is consistent with the hypothesis that macrophages interact differently with Ly⁺, and that this contributes to the ability of only live Ly⁺ to induce protective immunity.