Differential secretion of IL-12 and IL-18 based on intracellular localization of Listeria monocytogenes (44.2)

Abstract

Listeria monocytogenes (LM) is a gram-positive, intracellular bacterium that is commonly used to investigate the immune response to infection. Pro-inflammatory cytokines, such as IL-12 and IL-18, are secreted during LM infection to promote clearance of the bacteria through the induction of IFN-γ. LM secretes listeriolysin O (LLO) which allows the bacterium to invade the cytoplasm. Neither heat-killed LM (HKLM) nor LLO deficient LM (LLO−LM) actively produce LLO. When bone marrow derived macrophages (macs) and dendritic cells (DCs) are infected with LM, HKLM, or LLO−LM and co-cultured with naïve splenocytes, only macs or DCs infected with LM are able to induce IFN-γ secretion. ELISA data demonstrates that IL-12 is secreted from LM, HKLM, or LLO−LM infected macs and DCs, but IL-18 is only secreted from macs and DCs infected with LM. Therefore, IL-12 can be secreted by macs and DCs regardless of cytoplasmic invasion of LM whereas the secretion of IL-18 requires LM to gain access to the cytoplasm. When mice are infected with HKLM, there is no detectable IFN-γ secretion and this can be attributed to a lack of both IL-12 and IL-18. This implies that IL-12 is induced differently in response to HKLM in vivo versus in vitro. Further studies are ongoing to determine which pattern recognition receptors and cell types are responsible for recognizing and secreting IL-12 and IL-18 during in vivo LM infection. Supported by NIH AI064592.