MyD88 deficiency markedly worsens tissue inflammation and bacterial clearance in mice infected with Treponema pallidum, the agent of syphilis

PLoS One. 2013 Aug 5;8(8):e71388. doi: 10.1371/journal.pone.0071388. Print 2013.

Abstract

Research on syphilis, a sexually transmitted infection caused by the non-cultivatable spirochete Treponema pallidum, has been hampered by the lack of an inbred animal model. We hypothesized that Toll-like receptor (TLR)-dependent responses are essential for clearance of T. pallidum and, consequently, compared infection in wild-type (WT) mice and animals lacking MyD88, the adaptor molecule required for signaling by most TLRs. MyD88-deficient mice had significantly higher pathogen burdens and more extensive inflammation than control animals. Whereas tissue infiltrates in WT mice consisted of mixed mononuclear and plasma cells, infiltrates in MyD88-deficient animals were predominantly neutrophilic. Although both WT and MyD88-deficient mice produced antibodies that promoted uptake of treponemes by WT macrophages, MyD88-deficient macrophages were deficient in opsonophagocytosis of treponemes. Our results demonstrate that TLR-mediated responses are major contributors to the resistance of mice to syphilitic disease and that MyD88 signaling and FcR-mediated opsonophagocytosis are linked to the macrophage-mediated clearance of treponemes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacterial Load
  • Female
  • Immunologic Deficiency Syndromes / genetics
  • Immunologic Deficiency Syndromes / immunology*
  • Immunologic Deficiency Syndromes / pathology*
  • Inflammation / genetics*
  • Inflammation / immunology
  • Inflammation / pathology
  • Macrophages / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid Differentiation Factor 88 / genetics*
  • Phagocytosis / genetics
  • Phagocytosis / immunology
  • Primary Immunodeficiency Diseases
  • Syphilis / genetics
  • Syphilis / immunology*
  • Syphilis / pathology
  • Treponema pallidum / growth & development
  • Treponema pallidum / immunology*

Substances

  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88

Supplementary concepts

  • MYD88 Deficiency