Divergence of Macrophage Phagocytic and Antimicrobial Programs in Leprosy

Dennis Montoya, Daniel Cruz, Rosane M.B. Teles, Delphine J. Lee, Maria Teresa Ochoa, Stephan R. Krutzik, Rene Chun, Mirjam Schenk, Xiaoran Zhang, Benjamin G. Ferguson, Anne E. Burdick, Euzenir N. Sarno, Thomas H. Rea, Martin Hewison, John S. Adams, Genhong Cheng, Robert L. Modlin

Research output: Contribution to journalArticle

111 Scopus citations

Abstract

Effective innate immunity against many microbial pathogens requires macrophage programs that upregulate phagocytosis and direct antimicrobial pathways, two functions generally assumed to be coordinately regulated. We investigated the regulation of these key functions in human blood-derived macrophages. Interleukin-10 (IL-10) induced the phagocytic pathway, including the C-type lectin CD209 and scavenger receptors, resulting in phagocytosis of mycobacteria and oxidized low-density lipoprotein. IL-15 induced the vitamin D-dependent antimicrobial pathway and CD209, yet the cells were less phagocytic. The differential regulation of macrophage functional programs was confirmed by analysis of leprosy lesions: the macrophage phagocytosis pathway was prominent in the clinically progressive, multibacillary form of the disease, whereas the vitamin D-dependent antimicrobial pathway predominated in the self-limited form and in patients undergoing reversal reactions from the multibacillary to the self-limited form. These data indicate that macrophage programs for phagocytosis and antimicrobial responses are distinct and differentially regulated in innate immunity to bacterial infections.

Original languageEnglish (US)
Pages (from-to)343-353
Number of pages11
JournalCell Host and Microbe
Volume6
Issue number4
DOIs
StatePublished - Nov 22 2009

Keywords

  • CELLBIO
  • MICROBIO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

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    Montoya, D., Cruz, D., Teles, R. M. B., Lee, D. J., Ochoa, M. T., Krutzik, S. R., Chun, R., Schenk, M., Zhang, X., Ferguson, B. G., Burdick, A. E., Sarno, E. N., Rea, T. H., Hewison, M., Adams, J. S., Cheng, G., & Modlin, R. L. (2009). Divergence of Macrophage Phagocytic and Antimicrobial Programs in Leprosy. Cell Host and Microbe, 6(4), 343-353. https://doi.org/10.1016/j.chom.2009.09.002