Eta-1 (Osteopontin): An Early Component of Type-1 (Cell-Mediated) Immunity

TLDR

Cell‑mediated (type‑1) immunity is essential for protection against intracellular pathogens and can cause organ‑specific autoimmune damage when over‑activated. A phosphorylation‑dependent interaction between Eta‑1’s amino‑terminal region and its integrin receptor induces IL‑12 expression, while a phosphorylation‑independent interaction with CD44 suppresses IL‑10 production. Mice deficient in Eta‑1 show severely impaired type‑1 immunity to HSV‑1 and Listeria, reduced IL‑12 and IFN‑γ, increased IL‑10, and fail to develop sarcoid‑type granulomas, proving that Eta‑1 is a key cytokine that drives efficient type‑1 responses by regulating macrophage IL‑12 and IL‑10 expression.

Abstract

Cell-mediated (type-1) immunity is necessary for immune protection against most intracellular pathogens and, when excessive, can mediate organ-specific autoimmune destruction. Mice deficient in Eta-1 (also called osteopontin) gene expression have severely impaired type-1 immunity to viral infection [herpes simplex virus–type 1 (KOS strain)] and bacterial infection ( Listeria monocytogenes ) and do not develop sarcoid-type granulomas. Interleukin-12 (IL-12) and interferon-γ production is diminished, and IL-10 production is increased. A phosphorylation-dependent interaction between the amino-terminal portion of Eta-1 and its integrin receptor stimulated IL-12 expression, whereas a phosphorylation-independent interaction with CD44 inhibited IL-10 expression. These findings identify Eta-1 as a key cytokine that sets the stage for efficient type-1 immune responses through differential regulation of macrophage IL-12 and IL-10 cytokine expression.