TY - JOUR KW - Cluster Analysis KW - E-Selectin KW - Gene Expression Profiling KW - Humans KW - Inflammation KW - Interferon-gamma KW - Interleukin-1beta KW - leprosy KW - Models, Biological KW - Mycobacterium lepraemurium KW - Neutrophil Infiltration KW - Oligonucleotide Array Sequence Analysis KW - Receptors, Fc KW - Signal Transduction KW - Skin KW - Thalidomide KW - Toll-Like Receptor 2 AU - Lee DJ AU - Li H AU - Ochoa MT AU - Tanaka M AU - Carbone R AU - Damoiseaux R AU - Burdick A AU - Sarno E AU - Rea T AU - Modlin RL AB -

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 1beta (IL-1beta). In vitro activation of Toll-like receptor 2 (TLR2), up-regulated in ENL lesions, triggered induction of IL-1beta, which together with interferon gamma 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.

BT - The Journal of infectious diseases C1 - http://www.ncbi.nlm.nih.gov/pubmed/20070238?dopt=Abstract DA - 2010 Feb 15 DO - 10.1086/650318 IS - 4 J2 - J. Infect. Dis. LA - eng N2 -

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 1beta (IL-1beta). In vitro activation of Toll-like receptor 2 (TLR2), up-regulated in ENL lesions, triggered induction of IL-1beta, which together with interferon gamma 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.

PY - 2010 SP - 558 EP - 69 T2 - The Journal of infectious diseases TI - Integrated pathways for neutrophil recruitment and inflammation in leprosy. UR - http://jid.oxfordjournals.org/content/201/4/558.full.pdf+html VL - 201 SN - 1537-6613 ER -