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*
Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105; and
Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
IL-10 plays an essential role in blocking cytokine production by
activated macrophages. To analyze the consequences of enforced
expression of IL-10 by macrophages on innate and adaptive immune
responses, we generated transgenic mice (macIL-10tg mice) expressing an
epitope-tagged IL-10 (Flag-IL-10) under control of the human CD68
promoter. Expression of Flag-IL-10 was constitutive and restricted to
macrophages, as shown by sorting splenocyte cell populations and
intracellular staining for IL-10. Transgenic macrophages displayed
suppressed production of TNF-
and IL-12 upon stimulation with LPS.
When macIL-10tg mice were challenged with LPS, serum levels of
proinflammatory cytokines were attenuated compared with controls.
Infection with Mycobacterium bovis bacille
Calmette-Guérin resulted in 
10-fold-higher bacterial loads
than in wild-type mice. Normal T and B cell responses were observed in
macIL-10tg mice, suggesting that macrophage-specific overexpression of
IL-10 predominantly acts in an autocrine/paracrine manner, resulting in
chronically deactivated macrophages that manifest an impaired ability
to control pathogens.
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