Inhibition of Maturation of Human Monocyte-Derived Dendritic Cells in a Patient with Mycobacterium Avium Infection

Abstract

Mycobacterium avium complex is a facultative intracellular pathogen that can cause pulmonary disease in immunocompromised individuals. Dendritic cells (DCs) play a central role in protective immunity against mycobacteria. Mycobacterium avium complex infects DCs but does not impair in vitro infected monocytes differentiation into DCs. A 54-year old woman affected by chronic graft-versus-host-disease (cGVHD) was referred to our Division of Dermatology. Immature DCs were generated from her monocytes. One week later she was hospitalized due to a lung infection with Mycobacterium avium complex. Monocyte-derived DCs during Mycobacterium avium infection expressed low levels of CD1a and CD80 as determined by flow cytometry. They also expressed high levels of CD83 and CD86, and when stimulated with LPS for 24 hrs they slightly up-regulated CD83 and did not produce IL12. When monocyte-derived DCs were obtained from the patient after having recovered from the Mycobacterium avium complex infection, they expressed normal levels of CD1a and CD80 and were negative both for CD83 and for CD86. IL12 production in response to LPS was restored. Inhibition of DC maturation by the in vivo infection with Mycobacterium avium may be an immune-evasion mechanism used by the pathogen because incompletely matured DCs may not activate effector T cells efficiently in vivo.