Effects of interferon‐γ and Francisella tularensis elicited soluble factors on macrophage antigen processing

Abstract

Francisella tularensis is an intracellular pathogen that survives and replicates within the cytoplasm of macrophages (MØ) upon escape from the phagosome. In interferon‐γ (IFN‐γ) activated MØ, F.tularensis is unable to escape the phagosome and is directed to the endosomal‐lysosomal degradation pathway. IFN‐γ also up‐regulates MHC class II expression, but it is as yet unclear how it influences MØ antigen processing. In a cell line where class II expression is under the control of an IFN‐γ non‐responsive promoter, it was observed that IFN‐γ activation results in changes in the antigen processing and presentation pathway, leading to altered the T‐cell activation and cytokine production. Furthermore, IFN‐γ suppresses the fluid‐phase antigen uptake, but fails to alter Fc‐receptor‐mediated antigen uptake. These results suggest that IFN‐γ differentially alters the antigen uptake, to target antigen for differential processing and presentation. Interestingly, supernatant from F. tularensis infected MØ contain one or more soluble factors, which suppresses fluid‐phase antigen uptake, perhaps to alter antigen processing and presentation to skew T‐cell responses.PO1 # AI‐056320