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

• Published in: Journal of leukocyte biology Vol. 71; no. 1; pp. 80 - 88
• Main Authors: Wagner, Dirk, Sangari, Felix J., Kim, Sang, Petrofsky, Mary, Bermudez, Luiz E.
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.01.2002
• Subjects: Animals; Cells, Cultured; Humans; Interleukin-10 - immunology; Interleukin-12 - biosynthesis; Interleukin-12 - immunology; Listeria monocytogenes; Macrophages - immunology; Macrophages - microbiology; Mice; Mycobacterium avium; Mycobacterium avium - immunology; Transforming Growth Factor beta - immunology; transforming growth factor-^b1; Tuberculosis - immunology
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.71.1.80

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 ofmacrophages 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.