ARTD1 in Myeloid Cells Controls the IL-12/18-IFN-gamma Axis in a Model of Sterile Sepsis, Chronic Bacterial Infection, and Cancer

Kunze, Friedrich A.; Bauer, Michael; Komuczki, Juliana; Lanzinger, Margit; Gunasekera, Kapila; Hopp, Ann-Katrin; Lehmann, Mareike; Becher, Burkhard; Müller, Anne und Hottiger, Michael O. (2019): ARTD1 in Myeloid Cells Controls the IL-12/18-IFN-gamma Axis in a Model of Sterile Sepsis, Chronic Bacterial Infection, and Cancer. In: Journal of Immunology, Bd. 202, Nr. 5: S. 1406-1416

Abstract

Mice deficient for ADP-ribosyltransferase diphteria toxin-like 1 (ARTD1) are protected against microbially induced inflammation. To address the contribution of ARTD1 to inflammation specifically in myeloid cells, we generated an Artd1(Delta Myel) mouse strain with conditional ARTD1 deficiency in myeloid lineages and examined the strain in three disease models. We found that ARTD1, but not its enzymatic activity, enhanced the transcriptional activation of distinct LPS-induced genes that included IL-12, TNF-alpha, and IL-6 in primary bone marrow derived macrophages and LPS-induced IL-12/18-IFN-gamma signaling in Artd1(Delta Myel) mice. The loss of Artd1 in myeloid cells also reduced the T(H)1 response to Helicobacter pylori and impaired immune control of the bacteria. Furthermore, Artd1(Delta Myel) mice failed to control tumor growth in a s.c. MC-38 model of colon cancer, which could be attributed to reduced T(H)1 and CD8 responses. Together, these data provide strong evidence for a cell-intrinsic role of ARTD1 in myeloid cells that is independent of its enzymatic activity and promotes type I immunity by promoting IL-12/18 expression.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0022-1767
• Sprache: Englisch