Integrated pathways for neutrophil recruitment and inflammation in leprosy

Delphine J. Lee, Huiying Li, Maria T. Ochoa, Motoyuki Tanaka, Ryan J. Carbone, Robert Damoiseaux, Anne Burdick, Euzenir N. Sarno, Thomas H. Rea, Robert L. Modlin

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Neutrophil recruitment is pivotal to the host defense against microbial infection, but it also contributes to the immunopathology of disease. We investigated the mechanism of neutrophil recruitment in human infectious disease by means of bioinformatic pathways analysis of the gene expression profiles in the skin lesions of leprosy. In erythema nodosum leprosum (ENL), which occurs in patients with lepromatous leprosy and is characterized by neutrophil infiltration in lesions, the most overrepresented biological functional group was cell movement, including E-selectin, which was coordinately regulated with interleukin Iβ (IL-1β). In vitro activation of Toll-like receptor 2 (TLR2), up-regulated in ENL lesions, triggered induction of IL-1β, which together with interferon γ induced E-selectin expression on and neutrophil adhesion to endothelial cells. Thalidomide, an effective treatment for ENL, inhibited this neutrophil recruitment pathway. The gene expression profile of ENL lesions comprised an integrated pathway of TLR2 and Fc receptor activation, neutrophil migration, and inflammation, providing insight into mechanisms of neutrophil recruitment in human infectious disease.

Original languageEnglish (US)
Pages (from-to)558-569
Number of pages12
JournalJournal of Infectious Diseases
Volume201
Issue number4
DOIs
StatePublished - Feb 15 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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