Interleukin-4 regulates the expression of CD209 and subsequent uptake of Mycobacterium leprae by Schwann cells in human leprosy.
The ability of microbial pathogens to target specific cell types is a key aspect of the pathogenesis of infectious disease. Mycobacterium leprae, by infecting Schwann cells, contributes to nerve injury in patients with leprosy. Here, we investigated mechanisms of host-pathogen interaction in the peripheral nerve lesions of leprosy. We found that the expression of the C-type lectin, CD209, known to be expressed on tissue macrophages and to mediate the uptake of M. leprae, was present on Schwann cells, colocalizing with the Schwann cell marker, CNPase (2',3'-cyclic nucleotide 3'-phosphodiesterase), along with the M. leprae antigen PGL-1 in the peripheral nerve biopsy specimens. In vitro, human CD209-positive Schwann cells, both from primary cultures and a long-term line, have a higher binding of M. leprae compared to CD209-negative Schwann cells. Interleukin-4, known to be expressed in skin lesions from multibacillary patients, increased CD209 expression on human Schwann cells and subsequent Schwann cell binding to M. leprae, whereas Th1 cytokines did not induce CD209 expression on these cells. Therefore, the regulated expression of CD209 represents a common mechanism by which Schwann cells and macrophages bind and take up M. leprae, contributing to the pathogenesis of leprosy.
Teles
Rosane M B
RM
Division of Dermatology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA 90095, USA.
Krutzik
Stephan R
SR
Ochoa
Maria T
MT
Oliveira
Rosane B
RB
Sarno
Euzenir N
EN
Modlin
Robert L
RL
D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D054884:Host-Pathogen Interactions; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism*; D015441:Leprosy, Tuberculoid / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D009166:Mycobacterium leprae / Q000472:pathogenicity / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012583:Schwann Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D015854:Up-Regulation; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D015847:Interleukin-4; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin