CD74 deficiency is protective against P. aeruginosa-induced ocular keratitis (56.20)

Abstract Eye trauma and contact lens wear are the main factors that predispose to the development of infectious keratitis. The existing therapy often fails to control the excessive tissue damage that is induced during P. aeruginosa infection. While antibiotic treatment can reduce the bacterial burden, tissue damage occurs as a result of exaggerated local inflammation. Thus, a combined therapy including agents that control local inflammatory responses could be highly beneficial. We report that deficiency for CD74, the invariant chain for MHCII, appears protective against P.aeruginosa-induced corneal damage. This protection is exemplified with reduced bacterial burdens, and reduced pathology during infection. Since CD74 deficiency impairs MHCII-driven antigen presentation, changes in the CD4+ T cell maturation are expected. Consistently, the observed improved recovery of the CD74 KO could be due to alterations of the CD4+ T cell functions. However, about 8-10% of the CD74 is expressed on the cell surface, independently of the MHCII, where it forms complexes with CD44, and serves as s receptor for macrophage migration inhibitory factor (MIF). An alternative scenario to explain the lessened pathology would be a deficiency in the MIF-CD74 signaling axes. Consistently, MIF deficient mice are protected from P.aeruginosa-induced karatitis, suggesting that MIF-driven CD74-mediated activities exacerbate pathology during acute bacterial infection.