Mycobacterium avium infection of macrophages results in progressive suppression of interleukin-12 production in vitro and in vivo

Abstract

Interleukin-12 (IL-12) has been shown to have an important role in thehost defense against Mycobacterium avium. We sought todetermine if human monocyte-derived macrophages produce IL-12 uponM. avium infection. Although IL-12 can be measured insupernatants of M. avium-infected macrophages at 24, 48,and 72 h following infection, intracellular staining showed that24 to 48 h after infection, IL-12 was synthesized chiefly byuninfected macrophages in the monolayer, suggesting that M.avium infection inhibits IL-12 production. In addition, the dataalso suggest that the longer macrophage monolayers were infected, theless IL-12 they were able to produce. Stimulation of macrophages withIFN-γ prior to infection with M. avium resulted ingreater production of IL-12 compared with unstimulated macrophages. Culture supernatant of M. avium-infected macrophagemonolayers, but not control macrophages, partially inhibited IL-12production by IFN-γ-stimulated macrophages. This partial inhibitionwas not reversed by antiinterleukin-10 (anti-IL-10) andantitransforming growth factor β1 (anti-TGFβ1)-neutralizingantibodies. M. avium infection of macrophages in vitro alsosuppressed IL-12 synthesis induced by Listeriamonocytogenes infection. Immunohistochemistry staining of spleenof infected mice showed that IL-12 production by splenic macrophageswas more pronounced in the beginning of the infection but decreasedlater. Our data indicate that M. avium infection of macrophages suppresses IL-12 production by infected cells and that thesuppression was not a result of the presence of IL-10 and TGFβ1 inthe culture supernatant.